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Moura, Renata Kely de Paulo. "Avaliação in vitro das características de liberação de indometacina a partir de dispositivos oculares implantáveis". Universidade Federal da Paraíba, 2010. http://tede.biblioteca.ufpb.br:8080/handle/tede/6857.
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Previous issue date: 2010-08-31Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
The anatomy and physiology of the eye, together with its protective barriers represent challenges to effective ocular drug delivery systems. The pharmacological treatment of eye diseases had been limited to conventional drug formulations, which are not satisfactory for diseases affecting the posterior segment of the eye. The delivery of therapeutic doses at tissues from the posterior segment in order to minimize adverse systemic and regional effects is the main goal in the treatment of ocular diseases. With this aim, several studies have been conducted to develop new ocular drug delivery systems, such as those involving ocular implants. These implants are prepared using a variety of different polymers that can be either biodegradable or non-biodegradable. Polymers derived from lactic and glycolic acid have revealed to be promising materials for the formulation of ocular implants, mainly due to their biocompatibility and biodegradability. In this study, two different biodegradable indomethacin implants formulated based on a copolymer of lactic/glicolic acid (PLGA 50:50) and D,L-lactic acid (D,L-PLA) were characterized by differential scanning calorimetry (DSC), in vitro release using dissolution apparatus and scleral diffusion (from rabit´s eye) using Franz chambers. The study was done in collaboration with 3T Biopolymers (São Paulo, Brazil) that provided samples of the polymers and implants for analyses. The results of the validation of the HPLC method for indomethacin quantification were within the limits set forth by Brazilian legislation (RE 899, 2003, ANVISA). The results of DSC analysis revealed absence of any evidence of physico-chemical interactions between the drug and polymer. The suppression of the indomethacin melting peak is probably due to changes from the crystalline to the amorphous state of the drug following lyophilization or by dilution effects. Preliminary in vitro release data revealed a triphasic profile for indomethacin release from the PLGA-based implants and a biphasic one for the PLA implants. The implants formulated with PLGA promoted a faster release of indomethacin (103.64%) compared with implants formulated with PLA (49.9%) during the thirty days of the experiment. The release profile of indomethacin was determined by the rate of degradation of polymers, which also determined the scleral diffusion of indomethacin from PLGA and PLA (1.7 x 10-5 cm / s and 0.24 x 10-5 cm / s, respectively). The scleral diffusion experiments using Franz difusion chambers have shown that the rabit sclera is permeable to indomethacin and polarized light microscopy revealed that the structure of the scleral collagen fibers were not significantly altered during the diffusion experiments. The drug-release systems studied were able to release indomethacin in a sustained fashion, serving as a model for the formulation of indomethacin implants that could be used in the future for the treatment of ocular diseases such as the cystoid macular edema.
A anatomia e fisiologia do olho e suas barreiras protetoras representam um desafio para o desenvolvimento de sistemas de transporte de drogas oftálmicas efetivos. O tratamento farmacológico de doenças oculares tem se limitado às formas convencionais de administração que não são satisfatórias para o tratamento de doenças que acometem o segmento posterior do bulbo do olho. O transporte de doses terapêuticas para os tecidos do segmento posterior do olho, que minimize os efeitos colaterais sistêmicos e locais, é o principal objetivo no tratamento de doenças oculares. Visando atingir este objetivo, estudos têm sido feitos no sentido de desenvolver novos sistemas de liberação de fármacos para o olho, entre estes estão os implantes. Esses implantes são preparados a partir de diferentes polímeros, os quais podem ser biodegradáveis ou não biodegradáveis. Os polímeros derivados dos ácidos lático e glicólico têm se revelado bastante promissores devido, principalmente, às suas características de biocompatibilidade e biodegradabilidade. Neste trabalho, dois diferentes implantes de indometacina formulados a partir do copolímero ácido lático / ácido glicólico (PLGA 50:50) e do polímero derivado do ácido D,L-lático (PLA), através de liofilização da mistura polímero-fármaco, foram fornecidos pela empresa 3T Biopolímeros (São Paulo - SP) e avaliados através de DSC, estudos de liberação in vitro usando aparato de dissolução e estudos de difusão através de esclera de coelho utilizando câmaras de Franz. Os resultados da validação do método CLAE para quantificação da indometacina apresentaram-se dentro dos limites estabelecidos pela legislação brasileira (Resolução RE 899, 2003, ANVISA). As análises de DSC mostraram a ausência aparente de interações químicas e físicas entre o fármaco e os polímeros, sendo sugerido que o desaparecimento do pico de fusão da indometacina tenha ocorrido pela amorfização do fármaco durante o processo de liofilização ou pela diluição do fármaco no polímero. Os estudos preliminares de liberação in vitro demonstraram um perfil trifásico para os implantes formulados com PLGA e um perfil bifásico para àqueles formulados com PLA. Os implantes formulados com PLGA promoveram uma liberação mais rápida da indometacina (103,64%) quando comparado com os implantes formulados com PLA (49,9%) durante os trinta dias de experimento. O perfil de liberação da indometacina foi determinado pela velocidade de degradação dos polímeros, que também determinou a difusão escleral da indometacina a partir do PLGA e do PLA (1,7 x 10-5 cm/s e 0,24 x 10-5 cm/s, respectivamente). Os estudos de difusão escleral mostraram que a esclera de coelho é permeável à indometacina e a microscopia de luz polarizada mostrou que a estrutura das fibras colágenas da esclera não foram significativamente alteradas durante o estudo de difusão nas câmaras de Franz. Os sistemas de liberação de fármacos avaliados foram capazes de liberar a indometacina de forma prolongada, servindo como um modelo para formulação de implantes de indometacina que podem ser futuramente utilizados para tratamento de doenças como edema macular cistóide.
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Banerjee, Abhishek. "Functionalizable Biodegradable Polyesters for Drug Delivery Applications". University of Akron / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=akron1335240206.
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Friedrich, Nadja. "Integration dermaler Fibroblasten in PLGA-Scaffolds". Doctoral thesis, Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-130943.
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Die Wundheilung stellt einen physiologischen Vorgang zur Regeneration zerstörten Gewebes dar. Der reibungslose Ablauf der Heilung wird durch ein komplexes Zusammenspiel von Zellen und extrazellulären Komponenten gewährleistet. Durch vielfältige Faktoren kann dieser fein abgestimmte Prozess zum Erliegen kommen, so dass eine chronische Wundheilungsstörung resultiert. Trotz zahlreicher Behandlungsmöglichkeiten chronischer Wunden bleibt jedoch die erfolgreiche Heilung oftmals aus. Die Anwendung von biodegradierbaren Materialen (Biomaterialien) in der Wundheilung wurde in den vergangenen Jahren intensiv erforscht und teilweise erfolgreich am Patienten eingesetzt. An dem Ziel, ein Biomaterial herzustellen, welches alle funktionellen und strukturellen Fähigkeiten gesunder menschlicher Haut mit sich bringt, wird jedoch nach wie vor gearbeitet. In verschiedenen Studien konnte die gute Verträglichkeit und Biodegradierbarkeit des Biopolymers PLGA, bestehend aus Lactat und Glycolsäure, bereits gezeigt werden. In der vorliegenden Dissertation wurden dreidimensionale (3D)-Gerüste (Scaffolds) aus PLGA hinsichtlich ihrer Wechselwirkungen mit humanen dermalen Fibroblasten (Fb) untersucht. Dermale Fb leisten einen entscheidenden Beitrag zur erfolgreichen Wundheilung, da sie unter der Einwirkung diverser Wachstumsfaktoren zur Migration ins Wundgebiet sowie zur Neusynthese und Reorganisation extrazellulärer Matrix (ECM) befähigt sind. In den Untersuchungen wurden grundlegende Kenntnisse zum Verhalten der Zellen bezüglich Proliferation sowie Synthese nativer ECM in den PLGA-Scaffolds gewonnen und das Migrationsverhalten der Fb in das Biomaterial untersucht. Dabei zeigte sich, dass dermale Fb in den PLGA-Scaffolds nicht nur proliferieren sondern auch einen ausgeprägten Matrixstoffwechsel aufweisen. Sie sind in der Lage, Kollagen und Hyaluronsäure, wichtige Bestandteile der ECM, abzulagern. Zudem konnte mit Hilfe der Arbeit der Einfluss von Wachstumsfaktoren sowohl auf relevante ECM-Komponenten im 3D-Kultursystem als auch auf das Migrationsverhalten der Fb in das Biomaterial verdeutlicht werden. Aus den Ergebnissen geht hervor, dass 3D-PLGA-Scaffolds geeignete Substrate zur Kultivierung dermaler Fb darstellen. Die zukünftig geplante Weiterentwicklung und Funktionalisierung dieses Biopolymers für den Einsatz in der Wundheilung scheint somit viel versprechend.
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Bode, Corinna. "PLGA implants for ocular drug delivery". Thesis, Lille 2, 2019. http://www.theses.fr/2019LIL2S008.
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Jusqu'à aujourd'hui, le traitement des maladies oculaires postérieures, telles que la dégénérescence maculaire liée à l'âge, la rétinopathie diabétique et l'uvéite, reste difficile. L'œil avec ses différentes barrières oculaires est bien protégé des agressions extérieures. Ces barrières réduisent également la biodisponibilité des médicaments pour le vitré. Après une administration topique, seule une quantité limitée (0,001 - 0,0004 %) permet d'atteindre le vitreux. Ceci est causé par exemple par une dilution des larmes et une faible perméabilité cornéenne du médicament. Après une administration systémique ou orale, les barrières hémato-oculaires empêchent le médicament d'entrer et seulement environ 2 % du médicament administré se trouve dans le vitré. Afin d'atteindre des concentrations thérapeutiques, une dose élevée doit être administrée, ce qui augmente le risque d'effets secondaires. La façon la plus efficace de traiter les maladies postérieures restent l'injection intravitréenne. Cependant, de petites molécules lipophiles comme la dexaméthasone peuvent facilement se diffuser à travers la rétine et les barrières oculaires et ont donc une demi-vie limitée de quelques heures seulement. Étant donné que de nombreuses maladies postérieures sont chroniques, une injection intravitréenne fréquente serait nécessaire. Chaque injection comporte des risques de décollement de la rétine, d'hémorragie et d'autres effets secondaires. Les implants biodégradables pour administration intravitréenne peuvent prolonger la libération du médicament et en diminuer les effets secondaires. PLGA est un polymère largement utilisé qui est biocompatible et biodégradable. Il peut également soutenir la libération du médicament de quelques jours à plusieurs mois. Dans cette étude, les implants de formation in situ (ISFI) et les implants préformés préparés par extrusion à chaude ont été étudié en profondeur. L'objectif de ce travail était (i) d'étudier l'impact du volume du rejet (ii) évaluer le comportement de libération, de gonflement et de dégradation des implants préformés préparés avec différentes charges de médicament et différents types de polymères, (iii) visualiser la libération de médicament et l'absorption d'eau des implants préformés et de l'ISFI en utilisant des médicaments modèles colorés et (iv) étudier l'effet des quantités variables des différents additifs sur les caractéristiques essentielles de l'ISFI. Ces informations peuvent aider à fabriquer des implants avec différents profils de libération. Nos études montrent que l'ISFI est assez robuste en ce qui concerne les différents volumes de l'humeur vitreuse que l'on peut rencontrer in vivo. Cependant, le poids moléculaire et la concentration du polymère ont une forte influence sur la morphologie et le gonflement de l'implant. Par conséquent, la dégradation et la libération du médicament sont affectées. Pour les implants préformés, le gonflement "orchestre" la libération du médicament. Au début, seule une quantité limitée d'eau peut se diffuser dans les implants. Ainsi, seules des quantités insignifiantes du médicament sont dissoutes et peuvent être libérées. Lorsque le PLGA commence à se dégrader, le polymère devient plus hydrophile et de plus grandes quantités d'eau peuvent pénétrer. Ce gonflement du polymère facilite la dissolution et la diffusion du médicament et déclenche la libération du médicament. Les études utilisant des médicaments modèles colorés corroborent le rôle de la pénétration de l'eau et de la dissolution du médicament pour les implants préformés. En ce qui concerne l'ISFI, il a visualisé l'importance de la concentration du polymère sur la structure interne de l'implant qui en résulte et par conséquent l'absorption d'eau et la libération du médicament. Le comportement de gonflement et la morphologie de l'ISFI pourraient également être modifiés de manière significative en utilisant différents additifs. L'effet global sur la libération du médicament a été limitéUntil today, the treatment of posterior eye diseases, such as age-related macular degeneration, diabetic retinopathy and uveitis, remains challenging. The eye with its different ocular barriers is well protected from external factors. Those barriers also reduce the bioavailability of drugs to the vitreous. After a topical administration, only a limited amount (0.001 – 0.0004 %) reaches the vitreous. This is caused by for example reflexive blinking, tear dilution and a low corneal permeability of the drug. After a systemic or oral administration, the blood-aqueous and the blood-retinal barrier hinder the drug from entering and only around 2 % of the administered drug is found in the vitreous. In order to reach therapeutic concentrations, a high dose has to be given which in turn increases the risk for systemic side effects. The most efficient way to treat posterior diseases remains the intravitreal injection. However, small lipophilic molecules like dexamethasone can easily diffuse through the retina and the blood-ocular barriers and, thus, have a limited half-life of just a few hours. Since many of the posterior diseases are chronic, a frequent intravitreal injection would be necessary. Every intravitreal injection bears the risks for retinal detachment, hemorrhage, and other side effects. Biodegradable implants for intravi-treal administration can prolong the drug release and in turn decrease the side effects. Poly(lac-tic-co-glycolic acid) (PLGA) is a widely used polymer that is biocompatible and biodegrada-ble. It can also sustain the drug release from a few days up to several months. In this study, in-situ forming implants (ISFI) and pre-formed implants prepared via hot melt extrusion were studied in depth. The aim of this work was (i) to study the impact of the volume of the release medium, polymer type and concentration as well as drug content of different ISFI, (ii) to eval-uate the drug release, swelling and degradation behavior of pre-formed implants prepared with different drug loadings and polymer types, (iii) to visualize the drug release and water uptake of ISFI and pre-formed implants using colored model drugs and (iv) to investigate the effect of varying amounts of different additives on key features of ISFI. This knowledge can help to manufacture implants with different release profiles. Our studies show that ISFI are rather ro-bust regarding different volumes of the vitreous humor that could be encountered in vivo. How-ever, the polymer molecular weight and polymer concentration have a strong influence on the morphology and swelling behavior of the implants. Consequently, the degradation and drug release are affected. For pre-formed implants the swelling “orchestrates” the drug release. In the beginning only limited amounts of water can diffuse into the implants. Thus, only insignif-icant amounts of the drug are dissolved and can be released. When the PLGA starts to degrade, the polymer becomes more hydrophilic and bigger amounts of water can penetrate. This poly-mer swelling facilitates drug dissolution and diffusion and initiates the drug release. The studies using colored model drugs corroborate the role of water penetration and drug dissolution for pre-formed implants. Concerning ISFI, it visualized the importance of the polymer concentra-tion on the resulting inner implant structure and consequently the water uptake and drug release. The swelling behavior and morphology of ISFI could also be significantly altered using differ-ent additives. The overall effect on the drug release was limited
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Li, Zhongxuan. "Co-delivery of Two Growth Factors From Combined PLGA and PLLA/PCL Microsphere Scaffolds for Spinal Cord Injury Repairs". Thesis, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31200.
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The purpose of this study is to demonstrate the effectiveness of spheres-in-tube structured scaffolds to sequentially deliver two biomolecules during two phases of tissue regeneration following spinal cord injury (SCI). Scaffolds were synthesized of a poly (lactic-co-glycolic acid) (PLGA) base combined with Poly (L-lactic acid) / Poly (ε-caprolactone) (PLLA/PCL) microspheres.
The scaffolds are constructed by leveraging the different solubilities of PLGA, PLLA and PCL in super critical carbon dioxide and ethyl acetate during fabrication processes. Microspheres can reduce the pore size and porosity of PLGA scaffolds; this enhances their mechanical strength and enables them to provide long-term treatment without collapse.
The release of the epidermal growth factor (EGF) and basic fibroblast growth factor (FGF-b) are being used to study the release profiles of the designed scaffolds. The analysis shows that FGF-b is released from high porosity PLGA base as the first delivery vehicle and completes the release in the first week. PLLA or PCL microspheres, having the property of sustainably delivering encapsulated EGF in 36 days, are used as the second drug delivery vehicle.
FGF-b released within the first week can mimic biomolecules used to protect the surviving neurons and promote the development of sprout axons. The sustained release of EGF from microspheres is used for long-term therapy to differentiate multipotent cells into determined types at the injury site.
The results demonstrate that these enhanced parameters along with the ability of sequential co-delivery of growth factors, make these designed scaffolds a promising candidate in SCI studies.
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Mariño, Laura Victoria Español. "Aplicação da eletroforese capilar e cromatografia líquida de alta eficiência para a quantificação da dexametasona e diclofenaco em nanosuspensão". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/9/9139/tde-28052015-084712/.
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Os grandes desafios da medicina contemporânea destacam a necessidade de uma intensa pesquisa para desenvolver novos tratamentos para muitas doenças crônicas, tais como as reumáticas, que sejam efetivos, seguros e com qualidade. Uma das novas ferramentas para o desenvolvimento de novos medicamentos é a nanotecnologia, a qual nos últimos anos tem aumentado a sua aplicação na área farmacêutica contemplando um crescente otimismo acerca do seu potencial uso para obter melhores oportunidades de diagnóstico e de terapias mais eficazes. No presente trabalho foram encapsulados dois antiinflamatórios em sistemas nanoparticulados, nanoesferas de acido poli-láctico co-glicólico (PLGA), a técnica utilizada permitiu a encapsulação de compostos hidrofílicos e hidrofóbicos na mesma nanopartícula polimérica, diclofenaco de sódio (DS) e dexametasona (DX), respectivamente, obtendo nanopartículas com potencial para o tratamento de doenças inflamatórias crônicas. Para o desenvolvimento das nanoesferas se utilizou a técnica de emulsão/evaporação do solvente. As nanoesferas foram caraterizadas por microscopia eletrônica de varredura (SEM), microscopia eletrônica de transmissão (TEM), medição do pH, medição do tamanho de partícula, potencial zeta e polidisversividade e espectroscopia vibracional de infravermelho (IR). A eficiência de encapsulação (EE) dos fármacos (diclofenaco de sódio e dexametasona) nas nanoesferas foi realizada pelas técnicas analíticas, cromatografia líquida de alta eficiência (HPLC) e eletroforese capilar (CE), previamente validadas. Na melhor formulação foi obtida encapsulação de 51,4 ± 5,5 % para o diclofenaco e 66,9 ± 8,4 para a dexametasona.The great challenges of contemporary medicine emphasize the need for intensive research to develop new treatments for many chronic diseases, such as the rheumatic, to be effective, safe and of good quality. One of the new tools for the development of new drugs is the nanotechnology, which in recent years has increased its application in the pharmaceutical area contemplating a growing optimism about its potential use to get better opportunities for diagnosis and more effective therapies. In the present work were encapsulated two anti-inflammatories in nanoparticulate systems, nanospheres poly-lactic co-glycolic acid (PLGA), the technique used allows the encapsulation of hydrophilic and hydrophobic compounds in the same polymer nanoparticle, diclofenac sodium (DS) and dexamethasone (DX), respectively, obtaining nanoparticles with potential for the treatment of chronic inflammatory diseases. For the development of nanospheres the technique used was emulsion / solvent evaporation. The nanospheres were characterized by zeta potential infrared, particle size, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and pH. The encapsulation of the drug (diclofenac sodium and dexamethasone) in the nanospheres was performed by previously validated analytical techniques high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). In the best formulation was achieved encapsulation 51.4 ± 5.5% for diclofenac and 66.9 ± 8.4 for dexamethasone
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Sun, Yanqi. "Studies of PLGA Nanoparticles for Pharmaceutical Applications". Thesis, Cranfield University, 2014. http://dspace.lib.cranfield.ac.uk/handle/1826/9232.
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PLGA have already been successfully applied for controlled drug delivery systems by the pharmaceutical industry due to its biocompatibility, biodegradability and ease of processing. It has recently further been developed and formulated into a form of nanoparticle.
The single emulsion evaporation method was used to prepare nanoparticles in this study. By varying different parameters such as the concentration of regents, the type of surfactant and emulsion method, different particle sizes and size distribution of PLGA nanoparticles could be obtained.
The stability of PLGA nanoparticles was further investigated by assessing their thermal property over a certain period of time using DSC. The decrease of Tg confirmed the hydration and degradation of PLGA polymers and nanoparticles. The changes of surface morphology showed that the nanoparticles were in spherical shape and maintained smooth surface before the storage, whereas they started to lose their original shapes as well as agglomerate to each other after 2-week storage. These results suggested that there was an erosion and degradation of PLGA nanoparticles during storage.
Ibuprofen-loaded PLGA nanoparticles have been successfully prepared by o/w single emulsion evaporation method. During the stability study, a faster degradation rate compared to non-loaded PLGA nanoparticles was exhibited, showing that Ibuprofen increased the degradation rate of PLGA nanoparticles. According to the results of drug releasing study, PLGA nanoparticles exhibiting a slower drug release rate than pure drug which proved that drug-nanoparticule system could effectively increase the stability of drugs. PLGA polymer is a potential material for drug delivery system.
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Schardosim, Mariane Giacomini. "Confecção de estruturas tubulares permeáveis de PLGA". Pontifícia Universidade Católica do Rio Grande do Sul, 2012. http://hdl.handle.net/10923/3335.
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Previous issue date: nullPeripheral nerve injury accident is a common type of lesion that can cause loss of mobility and decrease the quality of life. Despite advances in the biomedical area, there are few cases where there is complete functional recovery of a damaged nerve. The application of biodegradable polymers such as poly(lactide-co-glycolide) (PLGA), shows a viable alternative of treatment in peripheral nerves injuries for presenting mechanical strength, biocompatibility and controlled degradation, being also an excellent material for drug delivery. A PLGA scaffold should be porous with pore sizes on the order of micro-and nanometer, which offers the possibility to insert growth factors, promoting a constant release of these biological structures. The aim of this research is to produce porous scaffolds of PLGA. This was achieved by dissolving the polymer in chloroform, adding a porogenic compound. A titanium rod with 2mm in diameter was deeped in the suspension obtained and dried in a hood, obtaining a layer of PLGA / porogen agent on the surface of the rod. In sequence, the rod was immersed in a solution of PLGA with chloroform. After dried for 2 hours in a hood, the titanium rods were submerged in deionized water for 48 hours, during which the water was changed every 8 hours in order to remove the porogenic agent. After this process, the tubular structures formed were easily removed from the rods. Finally, the prepared tubes were divided into groups and treated with different concentrations of sodium hydroxide, to create pores in the order of nanometers, and subsequently vacuum dried for 48 hours. The structures obtained were characterized by XRD, FTIR, SEM and the in vitro degradation was monitored by GPC.
Danos a nervos periféricos são formas comuns de lesões que podem causar perda de mobilidade e diminuir a qualidade de vida. Apesar dos avanços no campo biomédico, existem poucos casos em que há recuperação funcional completa de um nervo danificado. A aplicação de polímeros biodegradáveis tais como PLGA, apresenta uma alternativa viável no tratamento de lesões de nervos periféricos por possuir resistência mecânica, biocompatibilidade e degradação controlada. Uma matriz de PLGA deve apresentar poros na ordem de micrômetros e nanômetros, oferecendo a possibilidade de inclusão de fatores de crescimento e possivelmente promovendo uma libertação constante destas estruturas biológicas. O objetivo desta pesquisa é produzir matrizes porosas de PLGA. Isto foi realizado através da dissolução do polímero em clorofórmio, seguida da adição de um composto porogênico. Uma haste de titânio com 2mm de diâmetro foi imersa na suspensão obtida e quando retirada, foi seca em capela, obtendo uma camada de PLGA/agente porogênico na superfície da haste. Na sequência, a haste foi imersa em uma solução de PLGA com clorofórmio. Após seca durante 2h em capela, as hastes de titânio foram submersas em água deionizada durante 48h, durante as quais, a água foi trocada a cada 8h, para remoção do agente porogênico. Após este processo, as estruturas tubulares formadas são facilmente removidas das hastes. Finalmente, os tubos confeccionados foram divididos em grupos, e tratados com diferentes concentrações de hidróxido de sódio, para criação de poros na ordem de nanômetros, sendo, subsequentemente, secos em forno a vácuo durante 48h. As estruturas obtidas foram caracterizadas por XRD, FTIR, MEV e a degradação in vitro foi acompanhada por GPC.
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Maria, Adriana Del Monaco De. "Estudo do revestimento de modelos de stents coronários biorreabsorvíveis de PLLA com PLDLA/PLGA e ácido hialurônico". Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/98/98131/tde-04102017-140345/.
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A doença arterial coronariana vem sendo a maior causa de mortalidade no mundo, a angioplastia com implante de stent é uma estratégia importante nestes casos. Estudos apontam a biodegradabilidade, imobilização de antiproliferativos e moléculas bioativas nos stents, como características das futuras gerações destes dispositivos. Dentre estas, o ácido hialurônico contribui para a diminuição da agregação e proliferação de células entre as camadas da artéria e o dispositivo implantado. Foram desenvolvidos modelos de stents coronários biorreabsorvíveis de poli(-L-ácido láctico) (PLLA) com enxertia de ácido hialurônico (HA) em poli(-ácido lático co-ácido glicólico) (PLGA) e poli(L-D-ácido lático) (PLDLA). Os modelos foram caracterizados quanto suas propriedades térmicas, mecânicas e de superfície. O PLDLA e PLGA com enxertia de HA modificado com dihidrazida adípica (ADH) apresentaram características de superfície mais hidrofílicas, ideais para material de revestimento dos dispositivos. Desta forma, este trabalho possibilitou o desenvolvimento dos modelos físicos biorreabsorvíveis, com dimensões semelhantes aos stents coronários, feitos de PLLA, revestidos com PLGA e PLDLA com enxertia de HA e HAADH, e estáveis aos processos de esterilização por radiação ultravioleta e plasma de peróxido de hidrogênio.Coronary artery disease has been world´s leading cause of death and angioplasty stent implantation is an important strategy in these cases. Studies indicate that the biodegradability, immobilization of antiproliferatives and bioactive molecules in stents are characteristics of future generations of these medical devices. Amongst them, hyaluronic acid (HA) contributes to the decrease of the aggregation and proliferation of cells between artery layers and implanted device. For this purpose, poly (L-lactic acid) (PLLA) bioresorbable coronary stents with HA grafting in poly (lactic acid-co-glycolic acid) (PLGA) and poly (LD- (PLDLA) were developed. The models were characterized as their thermal, mechanical and surface properties. PLDLA and PLGA with adipic dihydrazide (ADH) modified HA grafting presented more hydrophilic surface characteristics, ideal as coating material of this devices. This project allowed the development of bioresorbable physical models with similar dimensions to coronary stents, made of PLLA, coated with PLGA and PLDLA with hyaluronic acid grafting, stable to ultraviolet radiation and plasma sterilization with hydrogen peroxide processes.
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El, Abbouni Sarah. "Microencapsulation of LL-37 Antimicrobial Peptide in PLGA". Digital WPI, 2016. https://digitalcommons.wpi.edu/etd-theses/235.
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Antimicrobial peptides are key actors in organisms€™ immune systems. They play an important role in phagocytosis, breaking bacteria membranes. They destroy the microbes, keeping them from repairing themselves, and therefore do not promote antimicrobial resistance. LL37 is a peptide produced by the human body. It is a short amino acid chain that is particularly active on the skin and mucous membranes. It has antimicrobial and fungal activity as well as wound healing properties, which makes it a very interesting active substance in wound treatment. However, its fragile and sensitive structure is a challenge to its use. Nowadays, encapsulation in a biocompatible polymer system is a promising technique in drug delivery, and presents a solution to LL37 administration and delivery. LL37 is a hydrophilic active substance, it will be trapped in PLGA (poly (lactic-co-glycolic acid)) by double emulsion and the microspheres will be shaped and stabilized by solvent evaporation. The capsules will be characterized by Dynamic Light Scattering (DLS) and Scanning Electron Microscopy. Their main features, drug loading, encapsulation efficiency and release profile, are determined using the Bradford assay. Since the peptide is expensive and delicate, it is important to optimize its encapsulation. For that reason, we will adapt the process to have the best drug loading as possible using water in oil in oil emulsions. For an external use, the capsules would be used over a few days, so having a fast release is very relevant. The larger the specific surface area, the faster the diffusion. For that reason, we will also study the impact of porosity on the release profile. As a result, different types of capsules will be synthesized, with higher porosity and by two processes: aqueous double emulsion and oil double emulsion. Their characteristic features and impact on bacterial pathogens will be determined and compared in order to determine their optimal synthesis process and formulation in given conditions of use.
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Janke, Julia [Verfasser]. "PLGA-Nanopartikel für die inhalative Vakzinierung / Julia Janke". Kiel : Universitätsbibliothek Kiel, 2014. http://d-nb.info/105939104X/34.
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Portes, Anne. "Formes à libération prolongée à base de PLGA". Paris 5, 1991. http://www.theses.fr/1991PA05P016.
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Vaidya, Pratik K. "Controlled Delivery of TGF-β1 from PLGA Nanoparticles". Cleveland State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=csu1355173781.
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Mondésert, Hugues. "Mineralization of PLGA nanofibers for periodontal tissue regeneration". Master's thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/15298.
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Mestrado em Ciência e Engenharia de MateriaisPeriodontal diseases induce a loss of soft and hard tissues surrounding the teeth after inflammation. Defects created by the infection would be replaced by the synthetic scaffold allowing progressive tissue regeneration. Mineralized PLGA (poly(lactic-‐co-‐glycolic acid)) nanofibers developed by electrospinningor jet spraying techniques are efficient biomaterials to maintain temporarily a physical structure and to enhance biocompatibility for hard tissue regeneration. The aim of this work was to mineralize PLGA nanofibers by two different methods: Simulated Body Fluid (SBF) immersion and projection by jet spraying (JS). SBF method consists in soaking PLGA matrices intohigh ions concentrated solutions (SBFx1 or SBFx5) to deposit mineral layers. With the new JS technique, we target a formation of a nanocomposite of PLGA and hydroxyapatite nanoparticles (nHA): first with the help of a blend solution (PLGA + nHA) directly projected (JS) and then with a simultaneous co projection of PLGA solution and nHA suspension in water (Co-‐JS). From material characterization perspective, samples produced by SBFx1 protocol showed a very weak mineral deposition, low crystalline sodium chloride whereas SBFx5 solutions allowed the formation of a consequent CaP mineral layer on electrospun PLGA matrices. SEM images allowed the observation of different mineral structures strongly depending on SBF concentration and immersion time. XRD patterns confirmed the presence of HA into JS PLGA matrices. Morphologically, JS scaffolds varied with the concentration of HA nanoparticles incorporated into the initial mixture. HA nanoparticles were successfully incorporated inside the polymer fibers with the first Jet spraying technique (JS) whereas nHAs were successfully deposited on the surface of the PLGA fibers with Co JS method.
A doença periodontal induz uma inflamação que pode levar à destruição dos tecidos de suporte do dente. A degradação provocada pela doença pode ser tratada com o recurso a suportes sintéticos que permitam a regeneração progressiva dos tecidos. As nanofibras de ácido polilactico co-‐glicolico (PLGA), mineralizadas, produzidas por electrofiação ou pela técnica de pulverização por jacto, são biomateriais adequados para funcionarem como suporte físico temporário e assegurarem a biocompatibilidade necessária à regeneração de tecidos. O presente trabalho tem como objetivo o estudo da mineralização de nano-‐fibras de PLGA para optimizar a regeneração de tecidos duros. São propostos dois métodos de mineralização: o método baseado no fluido fisiológico simulado (SBF) e o método baseado na pulverização por jacto (JS). A técnica de SBF consiste em mergulhar matrizes de PLGA, produzidas por electrofiação, numa solução concentrada de sais ao passo que a técnica de JS consiste em pulverizar uma suspensão preparada com nanopartículas de hidroxiapatite (Ca5(PO4)3(OH), HA) e uma solução polimérica. Os materiais produzidos foram caracterizados por difração de Raios-‐ X e por microscopia electrónica de varrimento (MEV).Para as amostras processadas pela técnica de SBF os resultados de DRX evidenciaram a presença de fosfatos de cálcio de baixa ristalinidade, correspondentes à fase de hidroxiapatite. As imagens de MEV permitiram observar a formação de estruturas minerais fortemente dependentes do tempo de imersão. Nas matrizes de PLGA tratadas por JS, a DRX confirmou a presença de HA e a MEV revelou que a morfologia das amostras depende da concentração das nanopartículas de HA adicionadas à solução polimérica inicial. O método de SBF permitiu uma deposição superficial de fosfatos de cálcio ao passo que, pelo método de JS, foi possível incorporar nanopartículas de HA no seio da matriz polimérica. A combinação dos dois métodos parece pois ser uma técnica promissora para fabricar suportes mineralizados para regeneração de tecido periodontal.
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Squarcia, Laura <1988>. "Enhanced topical delivery of dutasteride using PLGA nanoparticles". Master's Degree Thesis, Università Ca' Foscari Venezia, 2015. http://hdl.handle.net/10579/7001.
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Androgenic alopecia (AGA) is the most studied scalp disease, due to its diffusion among men an women; its cause is the conversion of testosterone to Dihydrotestosterone by the enzyme 5α-reductase type II, that is located in the hair follicle’s oil glands. The objective of this study was to investigate methods of topical application of Dutasteride, both type I and II 5α-reductase inhibitor, using PLGA particles as a delivery system, in order to avoid the side effects that an oral application could cause.
The skin is an efficient barrier and limits the skin permeation of exogenous substances, drugs included. Because of this property, it is difficult to deliver therapeutic agents through the skin and various chemicals has been studied as possible penetration enhancers or adsorption promoters.
Hair follicle drug delivery is an important pathway for dermal penetration, and could be a promising way to deliver drugs using nanoparticles.
Over the last two decades PLGA has generated great interest as a carrier for bioactive materials due to its excellent biocompatibility and biodegradability. Due to its lipophilic nature, dutasteride is well suited to PLGA encapsulation process.
Dutasteride-loaded PLGA (50:50)nanoparticles have been prepared using the nanoprecipitation method. It was anticipated that these particles allow dutasteride deposition in the pilosebaceous unit.
The size and morphology of the particles have been evaluated using scanning electron microscopy and dynamic light scattering. The dutasteride-loading efficiency had been determined using an analysis. Finally, a mixture of dutasteride-loaded PLGA nanoparticles and fitch-loaded PLGA nanoparticles have been used in order to study the efficacy and the depth of penetration in vitro, using a Franz diffusion cell and a confocal microscope.
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COLLICO, VERONICA. "development of PLGA hybrid nanoparticles for biomedical application". Doctoral thesis, Università degli Studi di Milano-Bicocca, 2017. http://hdl.handle.net/10281/153253.
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Tra tutti i polimeri biodegradabili conosciuti, l’acido polilattico-co-glicolico (PLGA) ha ricevuto una considerevole attenzione per le sue proprietà di biocompatibilità e biodegradabilità ed è ampiamente utilizzato come eccipiente nell’industria farmaceutica in quanto approvato dalla Food and Drug Administration (FDA) e dalla European Medicine Agency (EMA).
Il filo conduttore della tesi è l’utilizzo del polimero PLGA come nano-contenitore di particelle metalliche. Nanoparticelle inorganiche sono intrappolate nella matrice polimerica di PLGA (PLGA@metallo NPs) con il conseguente vantaggio di coniugare le affascinanti proprietà dei nanomateriali metallici con l'estrema biocompatibilità del polimero, al fine di rendere le particelle inorganiche attraenti nanocostrutti per una molteplicità di applicazioni biomedicali.
Il capitolo II della tesi mira allo sviluppo di un agente di contrasto (AC) per la risonanza magnetica nucleare (MRI) per la diagnosi precoce e il monitoraggio del decorso della malattia. A questo fine, la nanotecnologia offre un'opportunità unica per la progettazione di nuovi AC: la non-immunogenicità del PLGA, combinata con il comportamento paramagnetico delle particelle di manganese (MnO NPs) è capace di generare un contrasto T1-positivo nelle immagini di risonanza magnetica. Il costrutto PLGA@MnO NP è non tossico per le linee cellulari Hela e SVEC-4-10, e costituisce perciò un’attraente alternativa ai più tossici gadolinio e Teslascan. Inoltre, risultati promettenti ottenuti con MnO NPs funzionalizzate per il targeting attivo del morbo di Crohn, aprono la strada alla possibilità di coniugare l’agente di targeting anti-MadCAM-1 alla particella da noi sviluppata per una diagnosi MRI più accurata della malattia.
Applicando la metodica di incapsulamento di MnO NPs a particelle diverse per materiale, forma e dimensione, è stato messo a punto un protocollo universale di internalizzazione di particelle inorganiche in particelle di PLGA. Il metodo descritto è stato realizzato in collaborazione con il gruppo del professor Luis Liz-Marzan presso il CICBiomaGune, San Sebastian (Spagna). Il capitolo III è focalizzato sul caricamento di particelle di oro, ferro e Cd/Se nella matrice di PLGA. Per avere una miglior efficienza di incapsulamento è necessari avere particelle metalliche altamente concentrate e stabili in fase organiche. A tal fine sono stati sviluppati due approcci differenti per il trasferimento in solvente organico di particelle a base di oro: il metodo monobasico e bifasico. Entrambe le procedure sono traslabili a particelle di qualsiasi dimensione e forma.
I protocolli sviluppati mostrano strategie interessanti per la fabbricazione di nanostrutture ibride che uniscono i vantaggi della biodegradabilità ed elevata biocompatibilità del PLGA con le proprietà uniche delle nanoparticelle inorganiche, per ottenere nanosistemi adatti per numerose applicazioni in campo medico. Ad esempio, particelle d'oro plasmoniche in PLGA NPs possono essere impiegate per la terapia fototermica e la diagnosi; particelle di ossido di ferro intrappolate nel polimero potrebbero operare come agenti per ipertermia o diagnosi MRI; particelle di ossido di manganese caricate in PLGA NP hanno di dimostrato ottime proprietà come AC.
Prospettive future prevedono la funzionalizzazione dei nanocostrutti preparati per implementare la loro efficacia come agenti teranostici.Above all biodegradable polymers, poly(lactide-co-glycolide acid) (PLGA) has received a considerable attention as excipientin pharmaceutical industry up to be approved by Food and Drug Administration (FDA) and European Medicine Agency (EMA). The main features of PLGA have been discussed in chapter I. The headline of this work is the application of PLGA polymer as nano-container for metal nanoparticles: inorganic-based NPs (PLGA@metalNPs) entrapped into PLGA nano-containers harness the fascinating properties of the metallic nanomaterials with the extreme biocompatibility of the polymer, to makeinorganic particlesvery attractive tools for future biomedical applications. The thesis focuses on two main tasks: to prepare PLGA@MnO nanocomposite for targeted imaging of Crohn’s disease, and to set up and generalize the gold NPs phase transfer procedure and the PLGA@metal NPs synthetic protocol. Chapter II concerns the development of a manganese-based contrast agent (CA) for MRI application in vivo to achieve a highly accurate diagnosis of the stadiation and follow-up of the disease. In this respect, nanomedicine offers a unique opportunity to design novel smart enhancers by combining the safety of PLGA polymer andthe paramagnetic behavior of manganese, to generate PLGA@MnO nanocomposites as promising T1-positivecontrast agent for MRI. PLGA@MnO NPsare safe for Hela and SVEC-4-10 cell lines and thus they are more attractive contrast agents compared to gadolinium and Teslascan, which are more toxic. In addition, the promising results obtained with biofunctionalized MnO NPs for the active targeting of Crohn’s disease have also suggested to conjugate PLGA@MnO NPs with anti-MAdCAM-1 to target mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) overexpressed in inflamed bowel sites to enhance further the spatial resolution of MR images in vivo. In view of the encapsulation of manganese-based particles, a general method to entrap inorganic nanoparticles in the PLGA matrix was investigated further through Chapter III. The method here discussed has been set up in collaboration with the Luis Liz-Marzan’s group at CICBiomaGune (Spain). The PLGA polymer has been exploited to trap metal NPs of different nature to make them safe for the human organismand at the same time to maintaintheir fascinating chemical-physical properties. PLGA NPs loading gold nanoparticles (spheres, rods and cages), iron oxide and quantum dots have been synthesized by single emulsion methodand characterized by Dynamic Light scattering and Transmission Electron Microscopy. Efficient encapsulation has been obtained by highly concentrated and stable metal NPs in organic solvent.To this purpose, two different approaches, the biphasic and the monophasic one, have been explored to transfer gold nanoparticles to organic solvent (iron and manganese-based NPs already meet these conditions). Both the procedures have been adapted to any size and shape of gold NPs. These general approaches are attractive strategies toward the fabrication of heterogeneous nanostructures based on inorganic platforms and functional cargo molecules (e.g. drugs, vaccines, nucleic acids, quantum dots, magnetic nanoparticles) located within the hydrophobic spacer. The hybrid particles join the advantages of the biodegradability and the high biocompatibility of PLGA polymer with the unique properties of inorganic nanoparticles, to obtain potential systems for numerous biomedical applications. PLGA loading plasmonic gold particles could be employed for phototermal therapy and diagnosis; iron oxide particles entrapped in the polymer NPs could act as hypertermic therapeutic agent or MRI contrast enhancers; manganese oxide nanoparticle-loaded PLGA NPs have been demonstrated to be a high performing CA. Future perspectives will be focused on the application of PLGA@inorganic NPs and their functionalizing particles with targeting moieties to enhance also their efficacy as theranostic agents.
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Ribeiro, Débora Amgarten. "Análise da resposta inflamatória à implantação de membranas de PLGA+lactamas e PLGA+nanopartículas de prata no tecido subcutâneo de ratos". reponame:Repositório Institucional da UFSC, 2016. https://repositorio.ufsc.br/xmlui/handle/123456789/167679.
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Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Odontologia, Florianópolis, 2016.Made available in DSpace on 2016-09-20T04:09:53Z (GMT). No. of bitstreams: 1 341274.pdf: 2062367 bytes, checksum: 9e2c31ae12105178caf4239749a1d515 (MD5) Previous issue date: 2016
As implicações biológicas da incorporação de agentes antibiofilmes às membranas utilizadas nas técnicas reconstrutivas de tecido ósseo não estão completamente esclarecidas. O objetivo deste estudo foi analisar a resposta inflamatória à implantação subcutânea de membranas de PLGA (ácido polilático co-glicólico) associadas a duas categorias de agentes antibiofilme: quatro tipos de lactamas e dois de nanopartículas de prata. Foram implantados, ao todo, 08 tipos de membranas (controles e testes) em 45 ratos Wistar adultos machos, distribuídos aleatoriamente nos períodos experimentais de 2, 7 e 30 dias. Cada animal recebeu 04 discos de membrana de 6mm de diâmetro, sendo que em todos os animais, 02 sítios obrigatoriamente receberam os discos controle (PLGA puro e colágeno) e os outros 02 sítios receberam, randomicamente, discos teste. Após cada período experimental, os animais foram anestesiados e submetidos a biópsias excisionais das áreas dos implantes e punção cardíaca (eutanásia) para a coleta de amostras de sangue e análise laboratorial - hemograma. As amostras removidas foram fixadas em formol, processadas e incluídas em parafina. A partir de cortes semi-seriados de 5 micrometros, foram confeccionadas as lâminas histológicas, coradas com HE para análise descritiva e semi-quantitativa da resposta inflamatória e biocompatilidade dos compostos testados. A membrana controle de colágeno foi a que mostrou maior reação tecidual ao longo dos 30 dias, com presença de macrófagos e células gigantes multinucleadas. As membranas testadas mostraram reação amena, muito semelhante entre si, e à membrana controle de PLGA puro. Dentro dos períodos experimentais testados, as amostras teste mostraram melhor resposta tecidual que as amostras controle.
Abstract : Biological aspects of the use of membranes for tissue reconstructive procedures embedded with anti-bacterial agents are not completely elicited. The aim of this study was to analyze the inflammatory response to subcutaneous implantation of bioabsorbable poly(lactic-co-glycolic acid) - PLGA membranes embedded with two different categories of anti-bacterial agents: four types of lactams and two silver nanoparticles. Collagen and pure PLGA membranes were used as control groups. Each animal randomly received 04 membranes, 02 of them necessarily the control discs. After 02, 07 and 30 days of implantation, the animals were anesthetized for the excisional biopsy of the implant areas and for blood sample collections through cardiac puncture (euthanasia). The skin samples were histologically processed and embedded in paraffin to undergo semi-serial cuts of 5 micrometers; these slides were stained using Hematoxylin-Eosin and descriptively analyzed by light microscopy. Semi-quantitative inflammatory response analyses of the tested compounds were also made. Both tested antibiofilm agents showed a similar mild reaction with a good resolution at the end of the experimental period. Within the experimental periods tested, the test samples showed better tissue response than the control samples.
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Oborná, Jana. "Řízené uvolňování léčiv z biodegradabilních hydrogelů". Doctoral thesis, Vysoké učení technické v Brně. Fakulta chemická, 2018. http://www.nusl.cz/ntk/nusl-385283.
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This dissertation is focused on the controlled release of drugs from a biodegradable amphiphilic hydrogel based on hydrophobic poly(lactic acid), poly(glycolic acid) and hydrophilic poly(ethylene glycol) (PLGA-PEG-PLGA, ABA) and its modification with itaconic anhydride (ITA). The resulting ,-itaconyl(PLGA-PEG-PLGA) copolymer is referred to as ITA/PLGA-PEG-PLGA/ITA or ITA/ABA/ITA. Itaconic acid provides reactive double bonds and a functional carboxyl group at the ends of the PLGA-PEG-PLGA copolymer chain, thereby rendering the modified ITA/ABA/ITA copolymer less hydrophobic and offering the possibility of forming a carrier for hydrophilic drug substances. These functional copolymers are thermosensitive and change in the external environment (e.g. temperature) causes a sol-gel phase transition due to the formation of micellar structure. The bioactive substances can thus be mixed with a copolymer which is in a low viscous phase (sol phase) and subsequently the mixture can be injected into patient's body at the target site where it forms a gel at 37 °C. This hydrogel becomes a drug depot, which gradually releases the active substance. Prediction of the substance’s release profile from the hydrogel is an effective tool to determine the frequency of administration, potentially enhancing efficacy, and assessment of side effects associated with dosing. The analgesic paracetamol and the sulfonamide antibiotic sulfathiazole were used as model drugs, representing hydrophilic and hydrophobic substances, respectively. The active substances had a significant effect on the resulting hydrogel stiffness. Type of solvent, incubation medium and nanohydroxyapatite also influenced on the gel stiffness and subsequent stability of the hydrogel-drug system. Controlled release of drugs took place in simulated conditions of the human body. Verification of Korsmeyer-Peppas (KP) drug-release model is also discussed in this thesis. The KP model was found suitable for simulating the release of sulfathiazole from ABA and ITA/ABA/ITA hydrogels. On the contrary, the performance of KP model was not suitable for describing the release of paracetamol from the ABA hydrogels. Therefore, a new regression model suitable for both buffered simulated media and water has been proposed. The proposed model fitted better the release of both sulfathiazole and paracetamol from composite material prepared from ABA hydrogel and nanohydroxyapatite.
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Quintilio, Wagner. "Apresentação de antígenos e liberação controlada como ferramentas para melhoramento para vacinas de segunda geração". Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-25102007-153335/.
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Esta tese envolveu o estudo de encapsulação de vacina bivalente contra difteria e tétano de uso adulto (dT) em microesferas de ácido poli(láctico-coglicólico) (PLGA), com o objetivo de desenvolver uma formulação que induzisse uma resposta protetora com um número reduzido de doses, ou preferencialmente de apenas uma dose. Para ter sucesso, uma formulação como tal deve ter um perfil de liberação de antígeno que simule as múltiplas doses que recebem o indivíduo. Assim, nesta tese são mostrados os resultados dos experimentos de caracterização bioquímica e imunológica da formulação citada, sem o uso de estabilizadores protéicos, a fim de reduzir a complexidade do sistema em estudo. Do ponto de vista das proteínas encapsuladas, tal caracterização envolveu estudos de fluorescência, de dicroísmo circular, de atividade antigênica e determinação por HPLC da degradação durante o processo de encapsulação. Do ponto de vista da formulação, foram realizados ensaios de degradação in vitro e de atividade imunogênica in vivo, em camundongos e cobaias. Os dados obtidos indicaram que a encapsulação em microesferas de PLGA de vacina dT, sem o uso de estabilizadores, permitiu a produção de uma formulação vacinal viável, capaz de estimular uma resposta imunológica protetora e de memória, abrindo caminho para o desenvolvimento da tecnologia de produção de vacinas polivalentes encapsuladas em microesferas de PLGA.The study on encapsulating a bivalent single dose vaccine against diphtheria and tetanus for adults (dT) within PLGA microspheres is described in this thesis. A successful single dose vaccine must show an antigen release profile mimicking the several doses a person should receive during the life. Therefore, results from the immunological and biochemical characterization of the formulation, prepared without protein stabilizers, is showed here. From the encapsulated protein point of view the characterization involved fluorescence, circular dichroism, antigenicity and HPLC analysis. From the formulation point of view, there were performed in vitro release assays and immunogenicity on mice and on guinea-pigs. The results indicated that the dT microencapsulation within PLGA microspheres without protein stabilizers lead to the production of a viable vaccine formulation, able to elicit protective and memory immune response.
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Raman, Harini. "Anorganic bovine hydroxyapatite-PLGA composites for bone tissue engineering". Lexington, Ky. : [University of Kentucky Libraries], 2005. http://lib.uky.edu/ETD/ukybien2005t00306/THESIS.pdf.
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Thesis (M.S.)--University of Kentucky, 2005.Title from document title page (viewed on November 8, 2005). Document formatted into pages; contains xi, 94 p. : ill. Includes abstract and vita. Includes bibliographical references (p. 83-93).
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Schlapp, Monika. "Kollagen/PLGA-Mikropartikel Komposite zur gesteuerten Freigabe von Gentamicin /". Aachen : Shaker, 2001. http://www.gbv.de/dms/bs/toc/32406716X.pdf.
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Fay, François. "Development of versatile drug delivery strategies using PLGA nanoparticles". Thesis, Queen's University Belfast, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.527933.
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Chinnakavanam, Sundararaj Sharath kumar. "IGF-I RELEASING PLGA SCAFFOLDS FOR GROWTH PLATE REGENERATION". UKnowledge, 2010. http://uknowledge.uky.edu/gradschool_theses/59.
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Growth plate is a highly organized cartilaginous tissue found at the end of long bones and is responsible for longitudinal growth of the bones. Growth plate fracture leads to retarded growth and unequal limb length, which might have a lifelong effect on a person’s physical stature. This research is a tissue engineering approach for the treatment of growth plate injury. Insulin-like growth factor I (IGF-I), which can stimulate cartilage formation, was encapsulated within PLGA microspheres that were then used to form porous scaffolds. The release profile of the IGF-I from the PLGA scaffold showed a biphasic release pattern. In vitro studies were done by seeding rat bone marrow cells (BMCs) on the top of IGF-I encapsulated PLGA scaffolds, and the results showed an increase in cell multiplication and glycosaminoglycan content. The final in vivo studies were conducted by creating growth plate injury and implanting scaffolds in the tibiae of the New-Zealand white rabbits. Histological analysis of tissue sections showed regeneration of cartilage, albeit with disorganized structure, at the site of implantation of IGF-I encapsulated scaffolds. This work will be a significant step towards tissue engineering of growth plate cartilage.
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Hilliard, Randall K. "ORIENTATION-SPECIFIC IMMOBILIZATION OF BMP-2 ON PLGA SCAFFOLDS". UKnowledge, 2007. http://uknowledge.uky.edu/gradschool_theses/463.
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A variety of synthetic bone graft materials such as the polymer poly(lactic-co-glycolic acid) (PLGA) have been investigated as alternatives to current tissue based bone graft materials. In this study, efforts have been made to improve the tissue-PLGA interface by immobilizing bone morphogenetic protein-2 (BMP-2) in an oriented manner on scaffolds using covalently immobilized heparin. The results demonstrated a four-fold increase in covalently immobilized heparin compared to non-specific heparin attachment. Furthermore, the scaffolds with covalently attached heparin retained approximately three-fold more BMP-2 than did either scaffolds with no heparin attached or scaffolds with non-specific heparin attachment. The activity of scaffolds with BMP-2 immobilized in various manners was examined using an alkaline phosphatase assay on C3H10T1/2-seeded scaffolds. These results indicated approximately twice the amount of activity with scaffolds that had BMP-2 immobilized with covalently attached heparin than on scaffolds with adsorption of BMP-2 and a three-fold increase in activity when compared to scaffolds that had non-specific heparin attachment as the mechanism for BMP-2 immobilization. These results demonstrated that PLGA with covalently linked heparin has potential to immobilize BMP-2 in a specific orientation that is favorable for cell-receptor binding, leading to the more efficient use of the bone-growth factor.
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Schardosim, Mariane Giacomini. "Confec??o de estruturas tubulares perme?veis de PLGA". Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2012. http://tede2.pucrs.br/tede2/handle/tede/3218.
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Previous issue date: 2012-08-22Peripheral nerve injury accident is a common type of lesion that can cause loss of mobility and decrease the quality of life. Despite advances in the biomedical area, there are few cases where there is complete functional recovery of a damaged nerve. The application of biodegradable polymers such as poly(lactide-co-glycolide) (PLGA), shows a viable alternative of treatment in peripheral nerves injuries for presenting mechanical strength, biocompatibility and controlled degradation, being also an excellent material for drug delivery. A PLGA scaffold should be porous with pore sizes on the order of micro-and nanometer, which offers the possibility to insert growth factors, promoting a constant release of these biological structures. The aim of this research is to produce porous scaffolds of PLGA. This was achieved by dissolving the polymer in chloroform, adding a porogenic compound. A titanium rod with 2mm in diameter was deeped in the suspension obtained and dried in a hood, obtaining a layer of PLGA / porogen agent on the surface of the rod. In sequence, the rod was immersed in a solution of PLGA with chloroform. After dried for 2 hours in a hood, the titanium rods were submerged in deionized water for 48 hours, during which the water was changed every 8 hours in order to remove the porogenic agent. After this process, the tubular structures formed were easily removed from the rods. Finally, the prepared tubes were divided into groups and treated with different concentrations of sodium hydroxide, to create pores in the order of nanometers, and subsequently vacuum dried for 48 hours. The structures obtained were characterized by XRD, FTIR, SEM and the in vitro degradation was monitored by GPC.
Danos a nervos perif?ricos s?o formas comuns de les?es que podem causar perda de mobilidade e diminuir a qualidade de vida. Apesar dos avan?os no campo biom?dico, existem poucos casos em que h? recupera??o funcional completa de um nervo danificado. A aplica??o de pol?meros biodegrad?veis tais como PLGA, apresenta uma alternativa vi?vel no tratamento de les?es de nervos perif?ricos por possuir resist?ncia mec?nica, biocompatibilidade e degrada??o controlada. Uma matriz de PLGA deve apresentar poros na ordem de micr?metros e nan?metros, oferecendo a possibilidade de inclus?o de fatores de crescimento e possivelmente promovendo uma liberta??o constante destas estruturas biol?gicas. O objetivo desta pesquisa ? produzir matrizes porosas de PLGA. Isto foi realizado atrav?s da dissolu??o do pol?mero em clorof?rmio, seguida da adi??o de um composto porog?nico. Uma haste de tit?nio com 2mm de di?metro foi imersa na suspens?o obtida e quando retirada, foi seca em capela, obtendo uma camada de PLGA/agente porog?nico na superf?cie da haste. Na sequ?ncia, a haste foi imersa em uma solu??o de PLGA com clorof?rmio. Ap?s seca durante 2h em capela, as hastes de tit?nio foram submersas em ?gua deionizada durante 48h, durante as quais, a ?gua foi trocada a cada 8h, para remo??o do agente porog?nico. Ap?s este processo, as estruturas tubulares formadas s?o facilmente removidas das hastes. Finalmente, os tubos confeccionados foram divididos em grupos, e tratados com diferentes concentra??es de hidr?xido de s?dio, para cria??o de poros na ordem de nan?metros, sendo, subsequentemente, secos em forno a v?cuo durante 48h. As estruturas obtidas foram caracterizadas por XRD, FTIR, MEV e a degrada??o in vitro foi acompanhada por GPC.
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Holz, Juliana Pelisoli. "Preparação de micro e nanoesferas de PLGA com mentol". Pontifícia Universidade Católica do Rio Grande do Sul, 2012. http://hdl.handle.net/10923/3235.
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Previous issue date: 2012One area of nanotechnology of great interest is the formation of nanoparticles (nanospheres and nanocapsules) because it allows the development of controlled release formulations, in other words, those with the ability to properly release the actives agents. In such products, the active ingredient protected is gradually released through appropriate stimulus. There is a special interest in the preparation of nanoparticles of biodegradable polymers, for example, polyesters such as poly-lactic acid and glycolic and its copolymers, such as acid poly(lactic-co-glycolic) (PLGA), considering its biocompatibility and biodegradation. In this context, this study has as objective to produce nanospheres from the PLGA biodegradable polymer containing menthol through the technique of multiple emulsion/solvent evaporation. The prepared PLGA / menthol micro and nanospheres, presented mostly average diameters between 217 and 13,103 nm, Tg 41 °C and thermal stability up to 260 °C. The presence of menthol in the micro and nanospheres was demonstrated by the characterization techniques used, as well as the physical presence of menthol aroma perceptiple to the smell. At last, was made a preliminary valuation of the efficiency of incorporation of aroma, showing to be effective, since the micro and nanospheres with a higher concentration of menthol in its formulation demonstrated from the techniques used (relation between the heights of the bands of menthol and PLGA in IR and through the higher mass loss relative to the menthol in the TGA), present approximately 60% more menthol incorporated into the polymer matrix of these micro and nanoparticles in relation to others.
Uma das áreas da nanotecnologia de grande interesse é a da formação de nanopartículas (nanoesferas e nanocápsulas), pois permite o desenvolvimento de fórmulas de liberação controlada, ou seja, aquelas com a capacidade de liberar os agentes ativos adequadamente. Em tais produtos, o princípio ativo protegido é liberado gradativamente por meio de estímulos adequados. Existe um interesse especial na preparação de nanopartículas de polímeros biodegradáveis, como por exemplo, os poliésteres como ácido poli-láctico e o glicólico, e seus copolímeros, como o ácido poli(láctico-co-glicólico) (PLGA), considerando sua biocompatibilidade e biodegradação. Neste contexto, o presente trabalho teve como objetivo produzir nanoesferas a partir do polímero biodegradável PLGA contendo mentol através da técnica de emulsão múltipla/evaporação do solvente. As micro e nanoesferas de PLGA/mentol preparadas apresentaram, na sua maioria, diâmetros médios entre 217 e 13. 103 nm, Tg 41 °C e estabilidade térmica até 260 °C. A presença de mentol nas micro e nanoesferas foi evidenciada através das técnicas de caracterização utilizadas, bem como, pela presença física de aroma característico de mentol perceptível ao olfato. Por último, foi feita uma avaliação preliminar da eficiência de incorporação do aroma, mostrando-se eficaz, uma vez que, as micro e nanoesferas com maior concentração de mentol em sua formulação demonstraram a partir das técnicas utilizadas (relação entre as alturas das bandas do mentol e de PLGA no IV e através da maior perda de massa relativa ao mentol no TGA), apresentarem aproximadamente 60% mais mentol incorporado a matriz polimérica destas micro e nanopartículas em relação às demais.
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SOUZA, Rebecca Ribeiro Torelli de. "Desenvolvimento e caracterização de micropartículas núcleo-coroa de PLGA". Universidade Federal de Pernambuco, 2012. https://repositorio.ufpe.br/handle/123456789/12727.
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CAPES; CNPq
A b-lapachona (b-lap) é um fármaco com diversas propriedades farmacológicas comprovadas, dentre elas atividade anticâncer. Entretanto, este fármaco apresenta baixo índice terapêutico acarretando em toxicidade para as células. Dessa forma, a incorporação da b-lap em sistemas de liberação controlada, tais como as micropartículas representa uma alternativa viável para a sua aplicação terapêutica. Assim, o objetivo deste estudo foi desenvolver e caracterizar microesferas núcleo-coroa de PLGA revestida por quitosana contendo -lap com propriedades bioadesivas para a administração oral e avaliar a cinética de liberação da -lap. As microesferas de PLGA foram preparadas pelo método de emulsão múltipla água em óleo em água seguido de evaporação do solvente e, posteriormente, revestidas por quitosana (CS), em diferentes concentrações, pelo método de adsorção (razão CS:PLGA 0:1, 0.3:1, 0.6:1 e 1:1, p/p). O perfil de liberação da b-lap a partir das microesferas foi avaliado simulando as condições gastrointestinais. As microesferas de PLGA revestidas por quitosana apresentaram eficiência de encapsulação da b-lap variando de 74% a 85% (razão b- lap:PLGA 1:15, p/p). As microesferas de PLGA exibiram tamanho de partícula de 6.14 μm (span de 2.38) e potencial zeta de -9.33 mV. Por outro lado, os sistemas microparticulados revestidos por quitosana apresentaram tamanho de partícula entre 5 - 7 μm com forma esférica e distribuição de tamanho homogênea (span de 2.00 – 2.84) e potencial zeta positivo, evidenciando a formação das microesferas núcleo-coroa. As análises de caracterização físico-química por FTIR, DSC e XRD sugeriram a formação de interação a nível molecular entre a b-lap e a matriz polimérica. A cinética de liberação da -lap a partir das microesferas exibiu um padrão de liberação bifásico, no qual o efeito burst foi influenciado pelo revestimento de quitosana nas microesferas, pois as microesferas de PLGA apresentaram maior efeito burst que as microesferas revestidas por quitosana. Ademais, os parâmetros cinéticos calculados pelo modelo exponencial mostrou que a liberação do fármaco a partir das microesferas CS:PLGA 1:1 favoreceram mudanças no padrão de liberação da -lap. Portanto, a microencapsulação da -lap em microesferas núcleo-coroa revestidas por quitosana representa uma alternativa para o desenvolvimento de sistema de liberação controlada administração por via oral devido às propriedades de gastroresistência e bioadesividade que facilitam sua captura pelo epitélio intestinal.
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Bouissou, Camille. "Encapsulation of an integrin-binding protein into PLGA microspheres". Thesis, University of Bath, 2006. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.432835.
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Narvekar, Priya P. "Axitinib Loaded PLGA nanoparticles for Age-Related Macular Degeneration". Scholar Commons, 2019. https://scholarcommons.usf.edu/etd/7866.
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Despite of all the research going on for the treatment of ocular diseases, age-related macular degeneration (AMD) remains one of the serious vision threatening disease worldwide. Choroidal neovascularization, a pathophysiological characteristic of wet AMD, is the growth of anomalous blood vessels in the eye choroidal layer. Neovascularization is a key factor in AMD and thus anti-angiogenic therapy is beneficial in reducing the development of new abnormal blood vessels to prevent progression of AMD. Axitinib, multi-receptor tyrosine kinase inhibitor, is a small molecule that works by blocking vascular endothelial growth factor receptors (VEGFR) and platelet derived growth factor receptors (PDGFR) responsible for developing neovascularization. Thus, goal of this study was to develop and characterise a sustained release formulation of Axitinib loaded poly (lactic-co-glycolic) acid (PLGA) nanoparticles. The nanoparticles were characterized for particle size and zeta potential as well as using DSC, TEM and in vitro drug release profile. The cytotoxicity of the formulation was evaluated on human retinal pigmented epithelium ARPE19 cells by MTT assay. The cellular uptake, anti-migration assay, and VEGF expression levels were found out in vitro using cells. The optimized formulation was 131.33 ± 31.20 nm in size with -4.63± 0.76 mV zeta potential. Entrapment efficiency was found to be 87.9 ± 2.7%. The cytotoxicity of ARPE19 cells was less than 12% for nanoparticles suggesting the in vitro compatibility at 10 µM concentration of drug. Cellular uptake, anti-migration assay and VEGF expression levels for the nanoparticles had greater uptake, had significant anti-angiogenic potential and exhibited inhibition of VEGF activity. The results showed successful development of axitinib loaded PLGA nanoparticles as an alternative potential treatment option for AMD.
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Iselin, Jacob A. "Surface Modification of PLGA Electrospun Scaffolds for Wound Healing and Drug Delivery Applications". University of Akron / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=akron1226012558.
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STECANELLA, Luciano Aparecido. "Desenvolvimento e caraterização de nanopartículas poliméricas contendo grandisina". Universidade Federal de Goiás, 2011. http://repositorio.bc.ufg.br/tede/handle/tde/2118.
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Previous issue date: 2011-12-23Grandisin, a tetrahydrofuranic lignan produced by Virola surinamensis seeds and leaves, is popularly used to treat erysipelas, colic and dyspepsia, and is active against Schistosoma mansoni, Plasmodium falciparum, Leishmania donovani and Trypanosoma cruzi. It also antinociceptive, anti-inflamatory and potential for protective (dose dependent) activities, preventing cyclophosphamide induced chromosomal fragmentation, being considered a potencial anti-cancer candidate. The encapsulation of grandisin in polymeric nanocapsules can increase its solubility in aqueous media, allowing drug administration by intravenous route. In the presente work, polymeric nanocapsules containing grandisin were produced by nanoprecipitation method (or interfacial pre-formed polymer deposition). The average diameter of these nanocapsules were around 160 nm, PdI < 0,2, zeta potential -15,73 mV and grandisin load of 6,54%, with encapsulation efficiency of (EE%) 98%. Stability study, comprising 30 days under refrigeration (4ºC ± 1ºC), showed that physicochemical characteristics of the formulation (color, bluish translucency, etc.) were the same as compared to the nanocapsules dispersion originally produced, so there were no alterations such as deposition of residues and/or crystals, lumps formation, creamming or supernatant oil, droplets adhered to the glass, flocculation or phase separation. Regarding encapsulated grandisin, during stability test, there was a reduction of 6,4% of the total encapsulated drug. Drug release study showed quick liberation in the first 48h (30,54%) and then kept slower, because only 52% after 21 days. Polymeric nanocapsules containing grandisin, obtained in this work, showed potential to be a drug release system to administration by intravenous route.
A grandisina, uma neolignana tetraidrofurânica obtida das sementes e folhas da planta Virola surinamensis, é popularmente utilizada no tratamento de erisipelas, cólicas e dispepsias, e possui ação comprovada contra Schistosoma mansoni, Plasmodium falciparum, Leishmania donovani e Trypanosoma cruzi. Apresenta também atividade antinociceptiva, anti-inflamatória e potencial ação quimioprotetora (dose dependente), prevenindo a fragmentação cromossômica induzida pela ciclofosfamida, sendo assim considerada potencial candidata a agente anti-câncer. A encapsulação da grandisina em nanocápsulas poliméricas pode aumentar sua solubilidade em meio aquoso, consequentemente, permitindo sua administração por via intravenosa. No presente trabalho foram produzidas nanocápsulas poliméricas contendo grandisina pelo método de nanoprecipitação (ou deposição interfacial de polímero pré-formado). Estas nanocápsulas apresentaram diâmetro médio em torno de 160 nm, PdI < 0,2, potencial zeta de 15,73 mV e carga de grandisina de 6,54%, com eficiência de encapsulação (EE%) de 98%. O estudo de estabilidade, realizado por um período de 30 dias sob refrigeração (4ºC ± 1ºC), mostrou que as características físicas da formulação (coloração, translucência azulada, etc.) foram mantidas em relação à dispersão de nanocápsulas originalmente produzida, não sendo observadas alterações como deposição de resíduos e/ou cristais, formação de grumos, cremagem ou nata sobrenadante, gotículas de óleo aderidas ao vidro, floculação ou separação de fases. Com relação à grandisina encapsulada, durante o estudo de estabilidade, foi verificada uma redução de 6,4% do total encapsulado. O estudo de liberação mostrou rápida liberação nas primeiras 48h (30,45%) e posteriormente manteve-se mais lenta, com 52% após 21 dias de ensaio. As nanocápsulas poliméricas contendo grandisina, obtidas neste trabalho, mostraram ser um potencial sistema de liberação para viabilizar uma forma de administração por via parenteral para esta substância.
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Kucukturhan, Aysu. "Bioactive Agent Carrying Plga Nanoparticles In Thetreatment Of Skin Diseases". Master's thesis, METU, 2012. http://etd.lib.metu.edu.tr/upload/12614551/index.pdf.
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The aim of this study was to develop drug delivery system based on poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles (NPs) to achieve personalized treatment of selected skin disorders, like photo-aging, psoriasis and
atopic dermatitis. Dead Sea Water (DSW) and Retinyl Palmitate (RP) were used as active agents and they were loaded in PLGA NPs prepared either as spheres or capsules by o/w or w/o/w methods. MgCl2 and bovine serum albumin (BSA)
served as model active compounds. The diameter of the NPs was found to be in the range of 280 - 550 nm. The entrapment efficiency (E.E.) was less than 1% for RP, DSW and MgCl2, and 41% for BSA. Loading of Cl- together with BSA doubled the E.E. value of Cl- . In situ release studies showed a burst in the first day and more than 85% of
the chloride content was released within a week. When the macromolecule BSA was encapsulated, a much slower and triphasic release profile was observed which continued for up to 80 days. In vitro tests were performed using L929 fibroblast cells. Results of MTT
(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) test revealed that none of the NPs were cytotoxic. Additionally, all particles were hemocompatible
with hemolytic activity <1.5%. L929 fibroblast and Saos 2 human osteosarcoma cells were used to study the uptake of NPs by the cells. Particles accumulate near the nucleus. The characterization and cell viability tests, and drug release behavior indicate the suitability of these NPs for further testing to develop a patient specific skin diseases treatment approach.
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Raman, Harini. "AN ORGANIC BOVINE HYDROXYAPATITE-PLGA COMPOSITES FOR BONE TISSUE ENGINEERING". UKnowledge, 2005. http://uknowledge.uky.edu/gradschool_theses/201.
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The objective of the present study was to synthesize porous, biodegradable poly (D, l- lactide-co-glycolide) PLGA-B-HA (Bovine hydroxyapatite) composite and evaluate the effect of ceramic content on bone marrow cell differentiation in vitro. A macroporous biodegradable PLGA-B-HA composite with the pore size varying from 0.1 to 1000?? and a highly interconnected structure was fabricated using the freeze-drying/lyophilization technique. A pilot study was done to determine the effects of B-HA on to the osteoblast function. The main study was done to determine the effect of the increase in B-HA concentration on to the mesenchymal stem cell differentiation. Morphological characteristics of the composites were analyzed using FTIR and SEM/EDX analysis. The composites were seeded with neonatal rat calvarial osteoblasts (NRCO). The polymer: ceramic ratio in this study was 35%:65%. For comparison parallel experiments involving pure HA-200 discs were performed. SEM results indicated a higher proliferation and mineralization on PLGA-B-HA composites than pure HA discs. In addition, we evaluated the in vitro characteristics of PLGA-B-HA composites with varying ratios, i.e., 1:1, 1:2 and 1:3, seeded with rat marrow cells. FTIR indicated an increase in the area under the ceramic peak as ceramic concentration was increased. In addition, the average roughness values increased in the order of 1:3 andgt; 1:2 andgt; 1:1. Both compressive strength and modulus of 1:1 were significantly higher than 1:2 and 1:3 PLGA-B-HA composites. No significant difference in compressive modulli and strengths could be observed for 1:2 and 1:3 PLGA-B-HA composites. Cellular activity was determined by measuring AP activity, total protein analysis and osteocalcin concentration. Evaluation of alkaline phosphatase activity showed bone cells attached to 1:3 (PLGA-B-HA) expressed significantly higher alkaline phosphatase as compared to 1:1 and 1:2 PLGA-B-HA composites. In addition, cells seeded on to 1:3 composites secreted significantly higher osteocalcin and at a relatively short time period as compared to the other samples. Corrosion studies (ICP) and pH values indicate minimal difference in the concentration of Ca and P and pH in tissue culture media for all the samples at the end of all time periods. Hence we conclude that an increase in the ceramic concentration stimulated mesenchymal stem cell differentiation thereby promoting osteogenesis.
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Holz, Juliana Pelisoli. "Prepara??o de micro e nanoesferas de PLGA com mentol". Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2012. http://tede2.pucrs.br/tede2/handle/tede/3192.
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Previous issue date: 2012-01-26One area of nanotechnology of great interest is the formation of nanoparticles (nanospheres and nanocapsules) because it allows the development of controlled release formulations, in other words, those with the ability to properly release the actives agents. In such products, the active ingredient protected is gradually released through appropriate stimulus. There is a special interest in the preparation of nanoparticles of biodegradable polymers, for example, polyesters such as poly-lactic acid and glycolic and its copolymers, such as acid poly(lactic-co-glycolic) (PLGA), considering its biocompatibility and biodegradation. In this context, this study has as objective to produce nanospheres from the PLGA biodegradable polymer containing menthol through the technique of multiple emulsion/solvent evaporation. The prepared PLGA / menthol micro and nanospheres, presented mostly average diameters between 217 and 13,103 nm, Tg 41 ?C and thermal stability up to 260 ?C. The presence of menthol in the micro and nanospheres was demonstrated by the characterization techniques used, as well as the physical presence of menthol aroma perceptiple to the smell. At last, was made a preliminary valuation of the efficiency of incorporation of aroma, showing to be effective, since the micro and nanospheres with a higher concentration of menthol in its formulation demonstrated from the techniques used (relation between the heights of the bands of menthol and PLGA in IR and through the higher mass loss relative to the menthol in the TGA), present approximately 60% more menthol incorporated into the polymer matrix of these micro and nanoparticles in relation to others
Uma das ?reas da nanotecnologia de grande interesse ? a da forma??o de nanopart?culas (nanoesferas e nanoc?psulas), pois permite o desenvolvimento de f?rmulas de libera??o controlada, ou seja, aquelas com a capacidade de liberar os agentes ativos adequadamente. Em tais produtos, o princ?pio ativo protegido ? liberado gradativamente por meio de est?mulos adequados. Existe um interesse especial na prepara??o de nanopart?culas de pol?meros biodegrad?veis, como por exemplo, os poli?steres como ?cido poli-l?ctico e o glic?lico, e seus copol?meros, como o ?cido poli(l?ctico-co-glic?lico) (PLGA), considerando sua biocompatibilidade e biodegrada??o. Neste contexto, o presente trabalho teve como objetivo produzir nanoesferas a partir do pol?mero biodegrad?vel PLGA contendo mentol atrav?s da t?cnica de emuls?o m?ltipla/evapora??o do solvente. As micro e nanoesferas de PLGA/mentol preparadas apresentaram, na sua maioria, di?metros m?dios entre 217 e 13.103 nm, Tg 41 ?C e estabilidade t?rmica at? 260 ?C. A presen?a de mentol nas micro e nanoesferas foi evidenciada atrav?s das t?cnicas de caracteriza??o utilizadas, bem como, pela presen?a f?sica de aroma caracter?stico de mentol percept?vel ao olfato. Por ?ltimo, foi feita uma avalia??o preliminar da efici?ncia de incorpora??o do aroma, mostrando-se eficaz, uma vez que, as micro e nanoesferas com maior concentra??o de mentol em sua formula??o demonstraram a partir das t?cnicas utilizadas (rela??o entre as alturas das bandas do mentol e de PLGA no IV e atrav?s da maior perda de massa relativa ao mentol no TGA), apresentarem aproximadamente 60% mais mentol incorporado a matriz polim?rica destas micro e nanopart?culas em rela??o ?s demais.
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Chang, Jiang. "Transferrin-PLGA nanoparticles applications to brain, glioma and trypanosoma targeting". Lille 2, 2009. http://www.theses.fr/2009LIL2S015.
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L'utilisation de nanoparticules pour la vectorisation de médicaments connaît un intérêt croissant en vue de diminuer les doses de médicaments administrés et de réduire leur toxicité. Dans le cadre de ce travail de thèse nous avons préparé des poly (D, L-lactide-co-glycolide) (PLGA) nanoparticules (NPs) biodégradables de taille de 80-nm en vue de les utiliser pour cibler les cellules surexprimant le récepteur de la transferrine (Tf-R). Lors de la préparation de ces nanoparticules nous avons montré que nous pouvions éviter l'utilisation de surfactants utilisés pour éviter l'agrégation des nanoparticules néoformées en ajoutant dans le milieu de synthèse des protéines comme la transferrine (Tf) ou la sérum albumine bovine (BSA). Ces protéines inhibent l'agrégation des nanoparticules en s'adsorbant sur leur surface. Des essais réalisés in vitro sur un modèle de la barrière hémato-encéphalique (BHE) ont montré que les Tf-NPs pouvaient pénétrer par endocytose de manière accrue et sélective la BHE en utilisant la voie des cavéoles. Les Tf-NPs activent peu le complément et ont un temps de demi-vie plasmatique chez le rat et la souris très important par rapport aux NPs seules. In vitro nous avons montré que l'endocytose de ces Tf-NPs par les cellules gliomateuses se faisait par la voie des cavéoles et que les monocytes ne les endocytosaient pas. Tous ces résultats confirment l'intérêt de tester in vivo la capacit?de ces Tf-NPs pour traiter les tumeurs cérébrales. Enfin la dernière partie de ce travail de thèse a ét?de tester l'activit?trypanocide des Tf-NPs chargées en diminazene-palmitate (DMZ-PAL). Les essais in vitro ont montré que les Tf-NPs permettaient une captation accrue des NP par trypanosoma brucei brucei (T. B. B. ) et augmentaient l'efficacité du médicament. Les essais in vivo mettent en évidence que les animaux infectés pouvaient être guéris en utilisant des doses moindres de principe actif. L'ensemble de ces résultats confirme l'intérêt de ce type de formulation pour traiter les tissus ou organes surexprimant le récepteur de la transférine
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Tonello, Andrea <1988>. "Synthesis and Engineering of PLGA-based Nanoparticles with antitumoral Properties". Master's Degree Thesis, Università Ca' Foscari Venezia, 2014. http://hdl.handle.net/10579/5394.
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Nano-based delivery systems have attracted a great deal of attention in the past two decades as a strategy to overcome the low therapeutic index of conventional anticancer drugs. Nanoparticles enable the delivery of a great variety of drugs including analgesics, anti-Alzheimer's drugs, cardiovascular drugs, and several macromolecules into the brain after intravenous injection of animals. The mechanism of nanoparticle-mediated drug transport across the blood-brain barrier appears to be receptor-mediated endocytosis followed by drug release within the endothelial cells. Modification of the nanoparticle surface with covalently attached targeting ligands lead to the adsorption of specific proteins after injection is necessary for this receptor-mediated uptake. A very critical and important requirement for nanoparticulate brain delivery is that the employed nanoparticles are biocompatible and, moreover, rapidly biodegradable, i.e. over a time frame of a few days. In addition to enabling drug delivery to the brain, PLGA-based nanoparticles, with bisabolol inside, may importantly reduce the drug's toxicity. Because of the possibility to treat severe central nervous system diseases such as brain tumors and to even transport proteins and other macromolecules across the blood–brain barrier, this technology holds great promise for a non-invasive therapy of these diseases.
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Courant, Thomas. "Nanoparticules incorporant des complexes inorganiques à visée diagnostique". Thesis, Reims, 2011. http://www.theses.fr/2011REIMS005/document.
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L’objectif poursuivi au cours de ce travail est l’encapsulation de complexes métalliques au sein de nanoparticules biocompatibles, et ce pour des visées diagnostiques. Dans ce but, un protocole de double émulsion-diffusion de solvant Wi/O/We, n’utilisant que des composés biocompatibles, a été mis au point et optimisé pour obtenir, de façon quantitative et reproductible, des nanoparticules de PLGA de diamètre compatible avec une injection par voie parentérale. Cette formulation a été employée avec succès pour l’encapsulation de complexes modèles de Cu(II). Les formulations optimales permettent d’obtenir des nanoparticules possédant des diamètres hydrodynamiques moyens inférieurs à 200 nm avec des efficacités d’encapsulation entre 20 et 25 %. L’utilisation de cette formulation pour l’encapsulation de chélates de gadolinium ne permet pas d’obtenir des rendements d’encapsulation satisfaisants. La modification du protocole vers une méthodologie Wi/O1/O2ne permet pas d’améliorer l’encapsulation et dénote l’absence d’affinités entre le polymère hydrophobe et les complexes hydrophiles. L’utilisation de nanoparticules composées d’une matrice hydrophile permet d’obtenir des taux de charges nettement supérieurs. Ceci conforte l’hypothèse selon laquelle les interactions entre le complexe et la matrice des nanoparticules jouent un rôle crucial pour l’encapsulationThe goal of this work was to encapsulate metal complexes into biocompatible nanoparticles for diagnostics. To reach this purpose, a double emulsion-solvent diffusion Wi/O/We technique was optimized, using only biocompatible compounds. It allowed the obtention of PLGA nanoparticles that are compatible with parenteral injections in a reproducible and quantitative way. This formulation was successfully applied to encapsulate model Cu(II)complexes. Optimal formulations showed mean diameters below 200 nm with encapsulation yields in the 20-25 % range. The use of this formulation for gadolinium chelates did not lead to satisfactory encapsulation yields. Thereafter, a Wi/O1/O2 methodology was developed but could not allow to raise the encapsulation efficiencies. This point showed the lack of affinity between the hydrophobic polymer and the hydrophilic chelates. The use of nanoparticles made of an hydrophilic matrix showed a ten-fold increase in the drug loading efficiency. This confirms the hypothesis in which interactions between chelates and nanoparticle matrices play a crucial role for encapsulation
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Albert, Claire. "Émulsions de Pickering biodégradables stabilisées par des nanoparticules de poly(acide lactique-co-glycolique) : étude physico-chimique et potentialité pharmaceutique". Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS491.
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Dans ce travail de thèse, nous avons formulé des émulsions de Pickering stables, biodégradables et biocompatibles stabilisées par des nanoparticules (NPs) de poly(acide lactique-co-glycolique) (PLGA). De telles émulsions sont une alternative, potentiellement moins toxique et irritante, aux émulsions conventionnelles stabilisées par des tensioactifs synthétiques. Dans un premier temps, une étude physico-chimique approfondie de ces systèmes a permis de clarifier leurs structures (macroscopique, microscopique et interfaciale) ainsi que leurs mécanismes et leurs cinétiques de stabilisation. Des études de la contribution du polymère stabilisant les NPs et des caractéristiques du polymère de PLGA utilisé sur les propriétés des émulsions ont également été réalisées. Cela a permis de mieux identifier les paramètres physico-chimiques clés nécessaires à une bonne stabilisation. Dans un second temps, nous nous sommes intéressés au potentiel pharmaceutique de ces émulsions pour une application topique. Des substances actives (SA), utilisées pour le traitement du psoriasis, ont été encapsulées avec succès dans les NPs (ciclosporine A et tacrolimus) et les gouttelettes de l’émulsion (calcitriol). Cette étude est un premier pas vers l’utilisation de ces émulsions pour la co-encapsulation de deux SA dans la même formulation : une première dans les NPs et une seconde dans les gouttelettes d’huile. La co-encapsulation devrait permettre d’améliorer l’observance du patient et pourrait conduire à un effet synergique entre les deux SAIn this thesis work, we formulated stable, biodegradable and biocompatible Pickering emulsions stabilized with nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA). Such emulsions are an alternative, potentially less toxic and irritating, to conventional emulsions stabilized with surfactants. Firstly, a thorough physico-chemical study of these systems was conducted in order to clarify their structures (macroscopic, microscopic and interfacial) as well as their mechanisms and kinetics of stabilization. Studies of the contribution of the polymer stabilizing the NPs and of the characteristics of the PLGA polymer on the properties of the emulsions were also carried out. This enabled a better identification of the physico-chemical key parameters responsible for a good stabilization. Secondly, we focused on the pharmaceutical potential of these emulsions for a topical application. Pharmaceutical active ingredients (API), used for the treatment of psoriasis, were successfully encapsulated in the NPs (cyclosporine A and tacrolimus) and the emulsion droplets (calcitriol). This study is a first step towards the use of these emulsions for the co-encapsulation of two API: one in the NPs and a second in the oil droplets. The co-encapsulation should improve patient compliance and could lead to a synergistic effect between the two API
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Calderini, Adriana. "Preparação e caracterização de nano-esferas de PLGA contendo 5-fluorouracil e estudo do acoplamento de quitosana e ácido fólico em sua superfície". [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/250353.
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Orientador: Francisco Benedito Teixeira PessineTese (doutorado) - Universidade Estadual de Campinas, Instituto de Química
Made available in DSpace on 2018-08-19T02:12:00Z (GMT). No. of bitstreams: 1 Calderini_Adriana_D.pdf: 8667238 bytes, checksum: 93c066670f54801635af79d770afae4c (MD5) Previous issue date: 2011
Resumo: 5-Fluorouracil (5-FU) e um dos fármacos mais úteis no tratamento de tumores sólidos em adultos, especificamente carcinomas do trato gastrointestinal (estômago, cólon e reto) e da mama. Em resumo, seu maior efeito bioquímico e a inibição da síntese do DNA, pois a concentração que inibe sua síntese pode ainda permitir a sintese do RNA. Causa severos efeitos adversos como mielo supressão, mucosite, dermatite, diarréia e toxicidade cardíaca. Em razão disto, têm sido realizadas várias tentativas para encapsular 5-FU a fim de reduzir os efeitos adversos que ele provoca. O objetivo deste projeto foi encapsular este anti-neoplásico utilizando nano-esferas de ácido poli(lático-co-glicólico), PLGA, como sistema carreador, acoplando à sua superfície quitosana e folato de quitosana para melhor endereçamento aos locais de ação, bioadesividade e menor toxicidade. A encapsulação de 5-FU em nano-esferas de PLGA foi aperfeiçoada através de planejamento experimental e por análise quimiométrica. Muitos fatores foram estudados: métodos de preparação, temperatura, quantidade inicial de 5-FU e pH. Na caracterização destes sistemas foram utilizadas diversas técnicas: espalhamento dinâmico de luz, determinação do potencial Zeta, calorimetria diferencial de varredura, análise termogravimétrica, difratometria de raios-X e microscopia eletrônica de varredura. Além disso, foram realizados ensaios de perfil de liberação, de estabilidade coloidal e estudo do comportamento desses sistemas em relação às células in vitro. O planejamento experimental permitiu obter nanoparticulas com capacidade de carregamento em torno de 11% e eficiência de encapsulação de 32%. O acoplamento de quitosana e folato de quitosana permitiu retardar a liberação do fármaco em solução. Para armazenagem destas partículas, observou-se que elas foram menos degradadas quando estão liofilizadas e mantidas a 4 °C. A melhor concentração de sacarose para liofilizá-las, sem que ocorra aumento de tamanho e polidispersão, foi 250 mmol/L. Os testes in vitro comprovaram a eficácia destas formulações
Abstract: 5-fluorouracil (5-fluoro-1H-pyrimidine-2,4-dione) is one of the most used drug to treat solid tumors in adults, specifically gastrointestinal (stomach and colorectal) and breast carcinomas. In summary, the major biochemical effect of 5-FU is inhibition of DNA synthesis, since concentrations which inhibit this synthesis may still permit RNA synthesis. It causes severe adverse effects as myelosuppression, mucositis, dermatitis, diarrhea and cardiac toxicity. Its encapsulation in nanoparticles can reduce these adverse effects, prolong its release and the drug can be placed directly on its site of action. The goal of this work was to encapsulate this anti-neoplasic drug using poly (lactic-co-glycolic acid) PLGA nanospheres as carrier system, attaching on their surface chitosan and folate-chitosan to attain an enhanced targeting, bioadesivity and less toxicity. The encapsulation of 5-FU in PLGA nanospheres was improved through an experimental design and chemometry. Many factors were studied: methods of preparation, temperature, initial amount of 5-FU and pH. In the characterization, many techniques were employed: dynamic light scattering, determination of Zeta potential, differential scanning calorimetry, thermo gravimetric analysis, X-ray difractometry and scanning electron microscopy. Besides, we also analyzed the release profile, colloidal stability and the behavior of these systems in relation to in vitro cancer cells. The experimental design allowed obtaining nanoparticles with drug loading around 11% and encapsulation efficiency of 32%. The attachment of chitosan and folate-chitosan also allowed prolonging the drug release in solution. To store these formulations, we observed that lyophilized particles kept at 4 °C were less degraded. The best sucrose concentration to freeze-drying these particles with no size and polidispersity change was 250 mmol/L. The in vitro tests proved the efficacy of these formulations
Doutorado
Físico-Química
Doutor em Ciências
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Suzuki, Isabella Luiz. "Viabilização da curcumina natural nanoencapsulada para inativação fotodinâmica". Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/76/76132/tde-01042016-143506/.
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Devido ao uso excessivo de antibióticos houve e ainda há um crescimento no número de cepas resistentes aos medicamentos existentes. Por causa desse crescimento de bactérias multirresistentes, o número de pesquisas que procuram alternativas terapêuticas antibacterianas tem aumentado, e dentre elas está a terapia fotodinâmica antimicrobiana ou inativação fotodinâmica (IFD). A inativação fotodinâmica, utilizada no controle biológico de microrganismos, envolve a ação de um fotossensibilizador (FS), ativado por um comprimento de onda específico, no intuito de oxidar substratos biológicos, resultando em efeito citotóxico. A cúrcuma ou curcumina natural, conhecida como açafrão da terra, consiste em mistura de três curcuminóides: curcumina, demetoxicurcumina e bis-demetoxicurcumina. A curcumina apresenta várias propriedades farmacológicas, no entanto, possui solubilidade extremamente baixa em soluções aquosas, que dificulta a sua utilização como agente terapêutico. O presente estudo propôs desenvolver nanopartículas poliméricas de PLGA contendo curcumina natural a fim de melhorar sua solubilidade e estabilidade, e também verificar sua eficácia na inativação fotodinâmica de microrganismos. As nanopartículas PLGA-CURC sintetizadas através da nanoprecipitação resultaram em três sistemas diferentes, com tamanho médio e eficiência de encapsulamento de 172 nm e 70% para PLGA-CURC1, 215 nm e 80% para PLGA-CURC2, e 242 nm e 80% para PLGA-CURC3. Testes de estabilidade mostraram proteção do polímero contra a degradação precoce da curcumina natural. Os ensaios microbiológicos in vitro com a solução de curcumina natural, as PLGA-CURC1 e PLGA-CURC2 foram eficientes na inativação da bactéria Gram-positiva Staphylococcus aureus, e do fungo Candida albicans. Porém, a solução apresentou toxicidade no escuro em altas concentrações, ao contrario das nanopartículas. O sistema PLGA-CURC2 com sua carga superficial modificada, gerou o sistema PLGA-CURC3, que inativou efetivamente a bactéria Gram-negativa Escherichia coli. Assim, concluiu-se que foi possível deixar a curcumina natural solúvel em água através do encapsulamento em nanopartículas de PLGA, certificar a melhora na estabilidade em meio aquoso (estocagem), além de inativar bactérias e fungo.Due to excessive over use of antibiotics there was and still are growth in the number of bacterial strains resistant to existing drugs. Because of the growth of multiresistant bacteria, the number of searches looking for alternatives antibacterial therapeutic has increased, and among them is the antimicrobial photodynamic therapy or photodynamic inactivation (PDI). The photodynamic inactivation used in biological control of microorganisms, involves the action of a photosensitizer (PS), activated by a specific wavelength in order to oxidize organic substrates, resulting in cytotoxic effect. Turmeric or natural curcumin, consists of a mixture of three curcuminoids: curcumin, demethoxycurcumin and bis-demethoxycurcumin. Curcumin has various pharmacological properties, however, has extremely low solubility in aqueous solutions, which makes the use as therapeutic agent harder. The present study aims to develop polymeric PLGA nanoparticles containing natural curcumin in order to improve their solubility and stability, and also verify its efficacy in photodynamic inactivation of microorganisms. The PLGA-CURC nanoparticles was synthesized by nanoprecipitation, resulting in three different systems, with an average size of 172 nm and 70% encapsulation efficiency for PLGA-CURC1, 215 nm and 80% for PLGA-CURC2, and 242 nm and 80 % for PLGA-CURC3. Stability tests showed the polymer protected the natural curcumin against premature degradation. Microbiological tests in vitro with the natural curcumin solution, the PLGA-CURC1 and PLGA-CURC2 were efficient in the inactivation of Gram-positive bacterium Staphylococcus aureus, and fungus Candida albicans. However, the solution presented dark toxicity at high concentrations, unlike the nanoparticles. The PLGA-CURC2 system with a modified surface charge, gave the PLGA-CURC3 system, which effectively inactivated Gram-negative bacterium Escherichia coli. Thus, it was concluded that it was possible to let curcumin water soluble by encapsulation in PLGA nanoparticles, to ensure improved stability in aqueous medium (storage), and to inactivate bacteria and fungus.
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Lee, Yan Sim. "The development of controlled-chemotherapy drug delivery system". Thesis, University of Bath, 2009. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.512304.
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The aim of this thesis was to develop biodegradable devices loaded with chemotherapy drug. The system is targeted for advanced ovarian cancer treatment through the intraperitoneal (IP) route of administration. Polylactide-co-glycolide (PLGA) was selected as the model biodegradable polymer to produce drug-loaded microsphere, hollow and solid fibres. Copolymer PLGA with three different lactic:glycolic acids ratios; 50:50, 65:35 and 75:25 were used in order to compare their drug loading capacities and in vitro drug release profiles. Cisplatin, a cytotoxic drug with proven activity against ovarian cancer was selected as the model chemotherapy drug. Intraperitoneal administration is often associated with abdominal pain therefore a local anaesthetic, lidocaine, was selected for the purpose of pain relief.
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Breier, Annette. "Grundlegende Untersuchungen zur Integration eines Wirkstofffreisetzungssystems in ein textiles Knochenimplantat am Beispiel des Antibiotikums Gentamicin". Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-181922.
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Das bei der Sanierung von großen segmentalen Knochendefekten bestehende Risiko einer fremdkörperassoziierten Infektion soll durch die Integration eines Wirkstofffreisetzungssystems in ein bestehendes textiles Knochenimplantat gemindert werden. Durch Immobilisierung des Wirkstoffs in eine degradierbare Polymermatrix wird eine zeitlich verzögerte Freisetzung bewirkt. Als Wirkstofffreisetzungssystem wird die Kombination von Polylactid (PLA) bzw. Poly(Lactid-co-Glycolid) (PLGA) als Matrixpolymer mit dem Antibiotikum Gentamicin als Wirkstoff untersucht, welches durch Beschichtung der textilen Scaffolds mittels Dip-Coating eingebracht werden soll. Es stehen die drei Beschichtungsmethoden „Suspension“, „Emulsion“ und „Schichtaufbau“ zur Auswahl, die jeweils über eigene Parameter zur Beeinflussung des Freisetzungsprofils verfügen. Die Methode „Suspension“ und die damit verbundenen Einflussfaktoren Korngröße, Korngrößenverteilung sowie Masseanteil des Antibiotikums und Schichtdicke der aufgetragenen Polymerschicht wurde als die günstigste herausgearbeitet. Im Teil II dieser Arbeit wird diese soweit optimiert, dass nahezu über den gesamten geforderten Zeitraum die festgelegte notwendige Dosierung aufrechterhalten werden kann. Erste in vitro Versuche weisen auf eine gute Zellverträglichkeit sowie eine ausreichende mikrobielle Wirksamkeit hinTo reduce the risk of infection in the treatment of long bone defects, a novel embroidered bone implant is to be provided with an antibiotic drug delivery system. Prolonged and controlled drug release can be achieved by coating the thread material with antibiotics incorporated in a degradable polymer matrix. The chosen drug delivery system is composed of polylactide acid (PLA) or poly(lactide-co-glycolide) acid (PLGA) as matrix polymer and the antibiotic gentamicin. It is integrated into the textile structure by dip-coating providing the three different methods suspension, emulsion and layered. Each method bears its appropriate parameters to influence the releasing profile. The suspension-method and its parameters grain size and grain size distribution as well as mass fraction of the antibiotic and the coating thickness could be proved as the most feasible. In part II of this essay the chosen coating set-up gets optimized so that a drug release nearly along the whole required term can be achieved. Preliminary in vitro studies show a good cell tolerance besides a sufficient microbial efficacy
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Perron, Josee Karine. "Development and characterization of PLGA 8515 scaffold for tissue engineering applications". Thesis, University of Ottawa (Canada), 2006. http://hdl.handle.net/10393/27282.
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This study reports the design, development, and characterization of 85/15 poly (dl-lactide-co-glycolide) acid (PLGA 85/15) scaffolds for tissue engineering applications. In this respect the effects of different processing parameters on the PLGA 85/15 scaffold's physical and mechanical properties were investigated. Porous PLGA 85/15 scaffolds were prepared using a gas foaming/salt leaching technique. The processing parameters under examination included gas saturation pressure, gas saturation time, and NaCl/polymer mass ratio. The physical properties of the scaffold considered were the density, the porosity, the average pore size, and the pore density. The mechanical property studied was the Young's modulus in compression. The results demonstrated that all the processing parameters worked in concert to produce a scaffold with a high level of interconnectivity. From the parameteric study, key processing parameters were identified and selected parameters led to optimal physical and mechanical properties of the scaffold. The experimental results obtained from the mechanical properties of scaffolds were compared with a theoretical model from Gibson and Ashby relating the scaffold's mechanical properties to the density. The predicted elastic responses of opened pores structure from the theoretical model showed agreement with the experimental results.
Subsequently, the effect of the optimized PLGA 85/15 scaffolds on the cell growth and the cell viability of the human promyelocytic leukemia cell line (HL-60) were reported. The investigation showed that the cell growth and viability were not impaired by the presence of PLGA 85/15 scaffolds for the time period under investigation.
Finally, the effects of different degradation media on the optimized PLGA 85/15 scaffold's physical and mechanical properties were also elucidated. The three different media were distilled water (dH2O), a phosphate buffered saline (PBS) solution, and HL-60 cells. In general, the average macropore size and the average molecular weight decreased as the degradation time increased in each medium. However, the scaffolds maintained mechanical and structural integrity throughout the study in all three media over the degradation period studied. Overall, PBS solution most strongly affected physical and mechanical properties, followed by dH2O and HL-60 cells. The distinct variations of the scaffold's properties using different media, demonstrated the importance of carefully selecting the medium to perform in vitro studies. The medium must replicate the actual environment where the scaffold would be used, in order to represent accurately the changes in properties that the scaffold would be undergoing.
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Joseph, Jamie William. "Oral delivery of glucagon-like peptide-1 using PLGA-COOH microspheres". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ46161.pdf.
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Wang, Shunfeng [Verfasser]. "Bioactive and Biodegradable PLGA-Biosilica Biomaterial for Bone Regeneration / Shunfeng Wang". Mainz : Universitätsbibliothek Mainz, 2019. http://d-nb.info/119083880X/34.
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Lohneis, Taylor Paige. "Consistent Fabrication of Ultrasmall PLGA Nanoparticles and their Potential Biomedical Applications". Thesis, Virginia Tech, 2019. http://hdl.handle.net/10919/95943.
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Nanotechnology and its potential for biomedical applications has become an area of increasing interest over the last few decades. Specifically, ultrasmall nanoparticles, ranging in size from 5 to 50 nm, are highly sought after for their physical and chemical properties and their ability to be easily transmitted though the bloodstream. By adjusting the material properties, size, surface potential, morphology, surface modifications, and more, of nanoparticles, it is possible to tailor them to a specific use in biomedical areas such as drug and gene delivery, biodetection of pathogens or proteins, and tissue engineering.
The aim of this study was to fabricate ultrasmall poly-(lactic-co-glycolic acid) nanoparticles (PLGA NPs) using a quick and easy nanoprecipitation method1, with some modifications, for general use in various biomedical areas. Nanoprecipitation of two solutions – PLGA dissolved in acetonitrile and aqueous poly(vinyl alcohol) (PVA) – at varying concentrations produced ultrasmall nanoparticles that range in size, on average, from 10 to 30 nm. By the data collected from this study, a selection method can be used to choose a desired PLGA nanoparticle size given a potential biomedical application. The desired nanoparticle can be fabricated using specific concentrations of the two nanoprecipitation solutions. Size of the ultrasmall PLGA NPs was characterized by dynamic light scattering (DLS) and confirmed by transmission electron microscopy (TEM). Spherical morphology of the PLGA NPs was also proved by TEM.
By generalizing the ultrasmall PLGA NP fabrication process, the idea is that these NPs will be able to be used in various biomedical applications depending on the goal of the furthered study. As an example of potential application, ~15 to 20 nm PLGA NPs were consistently fabricated for use as virus-like particle (VLP) scaffolds. Following formation, PLGA NPs were introduced to modified human papillomavirus (HPV) protein during protein refolding and assembly into virus-like particles (VLPs) via buffer exchange. The size of the VLPs was monitored with and without PLGA nanoparticles present in solution during the refolding process and TEM images were collected to confirm encapsulation.Master of Science
Nanotechnology, the manipulation of materials on an atomic or molecular scale, and its potential for biomedical applications has become an area of increasing interest over the last few decades. Nanoparticles, spherical or non-spherical entities of sizes approximately one-billionth of a meter, have been used to solve a wide variety of biomedical problems. For reference, a human hair is about 80,000 to 100,000 nm in size and the nanoscale typically ranges in size from 1 to 1000 nm. This size range is not visible to the naked eye, so methods of analysis via scientific equipment becomes paramount. Specifically, this study aims to fabricate ultrasmall nanoparticles, ranging in size from 5 to 50 nm, which are highly sought after for their physical and chemical properties and their ability to easily travel though the bloodstream. By adjusting the material properties, size, shape, surface charge, surface modifications, and more, of nanoparticles, it is possible to tailor them to a specific use in biomedical areas such as drug delivery, detection of viruses, and tissue engineering. The specific aim of this study was to fabricate ultrasmall poly-(lactic-co-glycolic acid) nanoparticles (PLGA NPs), a type of polymer, using a quick and easy nanoprecipitation method1, with some modifications. Nanoprecipitation occurs by combining two liquid solutions – PLGA and aqueous poly(vinyl alcohol) (PVA) – which interact chemically to form a solid component – a polymer nanoparticle. These two solutions, at varying concentrations, produced ultrasmall nanoparticles that range in size, on average, from 10 to 30 nm. Data collected from this study can be used to select a desired nanoparticle size given a potential application. The desired nanoparticle can be fabricated using specific concentrations of the two nanoprecipitation solutions. By generalizing the ultrasmall PLGA NP fabrication process, the idea is that these NPs can be used for a variety of biomedical applications depending on the goal of the furthered study. Two PLGA NP example applications are tested for in this work – in DNA loading and in encapsulation of virus-like particles (VLPs), which are synthetically produced proteins that can be neatly folded to resemble a virus. These VLPs can be used to as an alternative to live vaccines and they can be designed to stimulate the immune system. Positive initial results from this study confirm the potential of these nanoparticles to have a wide impact on the biomedical field depending on specific tailoring to a given application.
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Tsai, Max Chia-Shin. "Biodegradable paclitaxel-loaded plga microspheres for regional treatment of peritoneal cancers". The Ohio State University, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=osu1066335356.
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Das, Niladri mohan. "Development and characterisation of clindamycin hydrochloride loaded PLA/PLGA nanoparticles". Thesis, 2012. http://ethesis.nitrkl.ac.in/3218/1/niladrei_ethesis.pdf.
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Clindamycin hydrochloride drug most commonly used as antibiotics in dental and oral infection acts upon various bacterial infections also. In this experiment PLA and PLGA nanoparticle prepared and conjugated with Clindamycin hydrochloride drug. From these two nanoparticles PLGA shows good result. It is found through SEM and Zeta sizer study that these polymers after conjugation with clindamycin hydrochloride gaining mean particular size of 178.6 nm with zeta potential -17.5 mv. Due to very less zeta potential nanoparticles are remain far apart so no clumping found among the drugs. In DSC study it is shown that the Tg (glass transition temperature) of Clindamycin hydrochloride is about 1500C so it take time to disperse inside the body but after conjugation with PLGA its Tg getting reduced to about 480C.Due to this low glass transition temperature it can easily disperse inside the body. After conjugation with Clindamycin hydrochloride there also an investigation done through FTIR studies from which we got that there must be a good conjugation of clindamycin hydrochloride with PLGA nanoparticle. This is because the abundance of OH, C=O, group both are common in PLGA and Clindamycin hydrochloride drug. The stretching band in PLGA-clindamycin hydrochloride is 3644.32 cm-1 refers to the absence of hydrogen bond among the Clindamycin hydrochloride and PLGA which may stands for hydrophobic bond due to much abundance of OH group. At the end it can be tell that after conjugation there is no serious alteration of Clindamycin hydrochloride structure but due to very easily dispersible nature it can shows its bactericidal effect more rapidly in comparison to the conventional medicine which generally takes two to three days.
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Haripal, Gouri Shankar. "Preparation and characterization of PLA and PLGA scaffold and film". Thesis, 2012. http://ethesis.nitrkl.ac.in/3170/1/ethesis.pdf.
Texto completo da fonteResumo:
In this research, the PLA/PLGA scaffolds and films were prepared successfully from PLA/PLGA blank microparticles. The morphology of the PLA/PLGA scaffolds and films are characterized by means of SEM. Biodegradable and biocompatible scaffolds having a highly open porous structure and good mechanical strength are needed for cell proliferation, migration, and differentiation, and guidance for cellular in-growth. Biodegradable porous scaffolds can be surface engineered to provide an optical microenvironment for better cell adhesion and tissue in-growth. According to scanning electron microscopy (SEM), a 3-dimensional porous structure of films could be observed on the surface. As the morphology of PLA/PLGA scaffolds and films could not be stabilized, we investigated the effect of temperature and concentration of polymer on the properties of microporous scaffolds and films. The degradation of polymeric porous films occurs through a homogeneous hydrolytic chain cleavage mechanism and this process is altered by factors such as molecular weight and molecular weight distribution. So, the biocompatible film plays an important role in development of fully biodegradable, tissue compatible active wound dressing material.
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Yu, Chung-Fu, e 尤中甫. "STUDIES ON THE SYNTHESIS AND PROPERTIES OF THERMOSENSITIVE PLGA-PEG-PLGA TRIBLOCK COPOLYMERS". Thesis, 2009. http://ndltd.ncl.edu.tw/handle/08927080883991315848.
Texto completo da fonteResumo:
碩士大同大學
化學工程學系(所)
97
ABSTRACT In this study, a series of biodegradable triblock amphiphilic and thermosensitive PLGA-PEG-PLGA copolymers were prepared by using hydrophilic poly(ethylene glycol) (PEG) as macro-initiator and stannous octoate as a catalyst, lactide (LA) and glycolide (GA) via ring opening polymerization where the used PEG was equally weight ratio mixed with PEG1000 and PEG1500. This research was subdivided into three parts. In first part, a series of biodegradable triblock amphiphilic and thermosensitive PLGA-PEG-PLGA copolymers were prepared. Their molecular weight ratios of hydrophobic PLGA(X) and hydrophilic PEG (Y) were fixed at 2.5 and 3.0. In addition, the various molar ratios of LA and GA were designed. The effect of the different molar ratios of LA/GA on the aqueous properties, such as critical micellization temperature (CMT), critical micellization concentration (CMC), and sol-gel phase diagram etc, of the present triblock copolymers was investigated. In second part, a series of biodegradable triblock amphiphilic and thermosensitive PLGA-PEG-PLGA copolymers were prepared. Their molar ratio of LA and GA in the triblock copolymer was fixed at 75/25. The effect of different hydrophobic chain lengths in the PLGA-PEG-PLGA copolymers on the aqueous properties, such as critical micellization temperature (CMT), critical micellization concentration (CMC), and sol-gel phase diagram etc, of the present triblock copolymers was investigated. In third part, a series of biodegradable triblock amphiphilic and thermosensitive PLGA-PEG-PLGA copolymers were prepared. Their molar ratio of LA and GA in the triblock copolymer was fixed at 75/25 and hydrophobic chain length PLGA(X) and hydrophilic chain length PEG (Y) were fixed at 2.5. Then, these triblock copolymers was chain-end blocked with monomethoxy poly(ethylene glycol) (mPEG) to form mPEG-PLGA-PEG-PLGA-mPEG block copolymer and their aqueous properties and biodegradation behavior was investigated.