Artigos de revistas: "PLGA"

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Li, Qing, Yiling Zhang, Jingbing Li, Hao Wang, Hui Lu, Honghao Fan e Gang Zheng. "Stimulatory effects of poly-para-dioxanone, poly L-lactic acid, polycaprolactone, and poly(lactic-co-glycolic acid)/PLLA in rats". Materials Express 9, n.º 8 (1 de novembro de 2019): 962–69. http://dx.doi.org/10.1166/mex.2019.1582.

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Numerous fillers are increasingly used for augmenting volume loss and ameliorating facial wrinkles. Collagen stimulants are the most recent next-generation dermal fillers capable of inducing neocollagenesis. To investigate biophysical characteristics, the safety and efficacy of the newly developed combination, poly(L-lactide) or polyl-lactic acid (PLLA) and poly(lactide-co-glycolide) (PLGA), were compared with those of poly-para-dioxanone (PPDO), poly-l-lactic acid (PLLA), and polycaprolactone (PCL) fillers. PPDO, PLLA, PCL, or PLGA/PLLA was injected into the dorsal skin of 8-week-old rats. Tissue samples were obtained 0, 2, and 4 weeks post treatment for Sirius Red-staining, polarized light microscopy, enzyme-linked immunosorbent assay (ELISA), real-time reverse transcription PCR (qRT-PCR), and western blotting. The MagBeads Total RNA Extraction Kit was used to isolate total cell RNA. The PLGA/PLLA filler demonstrated similar neocollagenesis and inflammatory response as other collagen stimulants, and showed better biodegradability than PPDO, PLLA and PCL fillers. Our data suggest that the newly developed collagen-stimulating PLGA/PLLA filler may be a safe and effective option for correcting volume loss and rejuvenating photoaging skin.

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Jeong, Jieun, Sangsoo Yoon, Xin Yang e Young Jun Kim. "Super-Tough and Biodegradable Poly(lactide-co-glycolide) (PLGA) Transparent Thin Films Toughened by Star-Shaped PCL-b-PDLA Plasticizers". Polymers 15, n.º 12 (8 de junho de 2023): 2617. http://dx.doi.org/10.3390/polym15122617.

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To obtain fully degradable and super-tough poly(lactide-co-glycolide) (PLGA) blends, biodegradable star-shaped PCL-b-PDLA plasticizers were synthesized using natural originated xylitol as initiator. These plasticizers were blended with PLGA to prepare transparent thin films. Effects of added star-shaped PCL-b-PDLA plasticizers on mechanical, morphological, and thermodynamic properties of PLGA/star-shaped PCL-b-PDLA blends were investigated. The stereocomplexation strong cross-linked network between PLLA segment and PDLA segment effectively enhanced interfacial adhesion between star-shaped PCL-b-PDLA plasticizers and PLGA matrix. With only 0.5 wt% addition of star-shaped PCL-b-PDLA (Mn = 5000 g/mol), elongation at break of the PLGA blend reached approximately 248%, without any considerable sacrifice over excellent mechanical strength and modulus of PLGA.

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Taşkor Önel, Gülce. "Synthesis of L-ornithine- and L-glutamine-Linked PLGAs as Biodegradable Polymers". Polymers 15, n.º 19 (5 de outubro de 2023): 3998. http://dx.doi.org/10.3390/polym15193998.

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L-ornithine and L-glutamine are amino acids used for ammonia and nitrogen transport in the human body. Novel biodegradable synthetic poly(lactic-co-glycolic acid) derivatives were synthesized via conjugation with L-ornithine or L-glutamine, which were selected due to their biological importance. L-ornithine or L-glutamine was integrated into a PLGA polymer with EDC coupling reactions as a structure developer after the synthesis of PLGA via the polycondensation and ring-opening polymerization of lactide and glycolide. The chemical, thermal, and degradation property–structure relationships of PLGA, PLGA-L-ornithine, and PLGA-L-glutamine were identified. The conjugation between PLGA and the amino acid was confirmed through observation of an increase in the number of carbonyl carbons in the range of 170–160 ppm in the 13C NMR spectrum and the signal of the amide carbonyl vibration at about 1698 cm−1 in the FTIR spectrum. The developed PLGA-L-ornithine and PLGA-L-glutamine derivatives were thermally stable and energetic materials. In addition, PLGA-L-ornithine and PLGA-L-glutamine, with their unique hydrophilic properties, had faster degradation times than PLGA in terms of surface-type erosion, which covers their requirements. L-ornithine- and L-glutamine-linked PLGAs are potential candidates for development into biodegradable PLGA-derived biopolymers that can be used as raw materials for biomaterials.

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Denning, G. M. "IL-4 and IFN-gamma synergistically increase total polymeric IgA receptor levels in human intestinal epithelial cells. Role of protein tyrosine kinases." Journal of Immunology 156, n.º 12 (15 de junho de 1996): 4807–14. http://dx.doi.org/10.4049/jimmunol.156.12.4807.

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Abstract IL-4 and IFN-gamma increase release of secretory component (SC), the polymeric IgA (plgA)-binding segment of the plgA receptor (plgAR), by the human intestinal epithelial cell line HT29. Moreover, these two cytokines synergistically increase plgA binding and cell surface staining for the receptor. To understand better the mechanism by which these cytokines regulate plgAR, we did quantitative immunoblotting using Abs against secretory component. We found that synergy occurs at the level of total cellular plgAR. Additionally, time course studies indicated that maximal receptor levels required >24-h incubation, that reaching maximal levels required at least 18 h of cytokine treatment, and that receptor levels remained elevated as long as cytokines were present. Conversely, if cytokines were removed, then cellular plgAR levels decreased with an approximate t1/2 of 20 h. Finally, synergy required the simultaneous presence of both cytokines throughout the treatment period. Direct measurement of second messengers and inhibitor studies suggest that Ca2+, cAMP, protein kinase A, and protein kinase C do not play major roles in regulating cellular plgAR levels by either cytokine, and do not contribute to the mechanism of synergy. In contrast, protein tyrosine kinase inhibitors potently inhibited all cytokine-dependent increases in total cellular plgAR. These results suggest that IL-4 and IFN-gamma increase cellular plgAR levels in HT29 cells predominantly by activating protein tyrosine kinase-dependent signaling pathways.

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Rezende, Camila A. de, e Eliana Ap R. Duek. "Blendas de poli (ácido lático-co-ácido glicólico)/ poli (ácido lático): degradação in vitro". Polímeros 13, n.º 1 (janeiro de 2003): 36–44. http://dx.doi.org/10.1590/s0104-14282003000100009.

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Placas de copolímero de poli(ácido lactico-co-glicólico) têm sido produzidas e usadas como implantes que degradam e são absorvidos pelo organismo. Implantes que podem ser absorvidos apresentam vantagens em relação aos implantes metálicos. Nesse trabalho, foram obtidas placas a partir de blendas de poli(ácido lactico-co-glicólico)/ poli(ácido lático), (PLGA/PLLA) e caracterizadas durante o processo de degradação in vitro. Verificou-se que as blendas são imiscíveis e a estabilidade térmica das mesmas aumenta com a proporção de PLLA. O grau de cristalinidade também aumenta com a proporção de PLLA na amostra e com o tempo de degradação. Além disso, verificou-se que o PLGA degrada rapidamente e sua presença e quantidade modifica nitidamente a morfologia das blendas.

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Cardoso, M. Margarida, Inês N. Peca, Telma Lopes, Rui Gardner e A. Bicho. "Double-Walled Poly-(D,L-lactide-co-glycolide) (PLGA) and Poly(L-lactide) (PLLA) Nanoparticles for the Sustained Release of Doxorubicin". Polymers 13, n.º 19 (23 de setembro de 2021): 3230. http://dx.doi.org/10.3390/polym13193230.

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Double-walled nanoparticles (DWNPs), containing doxorubicin as a model drug, were produced using poly-(D,L-lactide-co-glycolide) (PLGA) and poly(L-lactide) (PLLA) by the solvent evaporation technique. Double-walled microparticles containing doxorubicin were also produced to make possible the examination of the inner morphology and drug distribution using optical and fluorescence microscopy. The produced microparticles present a double-walled structure with doxorubicin solubilized in the PLGA-rich phase. The DWNPs produced present very low initial burst values and a sustained DOX release for at least 90 days with release rates decreasing with the increase in the PLLA amount. Zero-order release kinetics were obtained after day 15. The results support that the PLLA layer acts as a rate control barrier and that the diffusion of doxorubicin from the drug-loaded inner PLGA core can be retarded by an increase in the thickness of the unloaded outer layer. The unloaded double-walled nanoparticles produced were used in in vitro tests with CHO cells and demonstrate that they are nontoxic, while the double-walled nanoparticles loaded with doxorubicin caused a great cellular viability and decreased when tested in vitro.

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K., Prakash Raj, Kathiresan K. e Pandian P. "A Review on Poly-Lactic-Co-Glycolic Acid as a Unique Carrier for Controlled and Targeted Delivery Drugs". Journal of Evolution of Medical and Dental Sciences 10, n.º 27 (5 de julho de 2021): 2034–41. http://dx.doi.org/10.14260/jemds/2021/416.

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In regulated and targeted drug distribution, biodegradable polymers have played a significant portion. Poly-lactic-co-glycolic acid (PLGA) has been an important desirable polymer in tissue engineering to meet a new drug delivery system. PLGAs, show a broad spectrum of erosion cycles and have tuning mechanical characteristics. Poly-lactic-co-glycolic acid (PLGA) has been the most successful polymeric biomaterial for use in controlled drug delivery systems. PLGA has been extensively studied, in particular, in the production of equipment for controlled distribution in industrial and research applications of small molecules, protein, and other macromolecules. PLGA is biocompatible and biodegradable, exhibits a wide range of erosion times, has tunable mechanical properties and most importantly, is a FDA approved polymer. PLGA has many properties such as controlled and sustained release, low cancerinducing, long-standing biomedical applications, biocompatibility with tissues and cells, and prolonged residence time. It is otherwise called as 'Smart Polymer' because improvements are fragile to conduct PLGA that has been widely examined in industrial and academic applications to produce instruments for the target delivery of tiny molecular drugs, proteins, and other large molecules. An introduction about the chemistry, physicochemical properties, manufacturing techniques of the devices, toxicity, and the reason influencing their decrease and release of the drug was given in the present study. Mathematical modelling is a useful tool for identifying, characterizing, and predicting the mechanisms of controlled release. Mathematical modelling applied against the target from PLGA – the devices has been clarified by discussing in the review, by explaining the underlying mathematical models and how this is used. KEY WORDS Biodegradable Polymers, PLGA, Biodegradability, Macromolecules

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Pek, Y. Shona, Pemakorn Pitukmanorom e Jackie Y. Ying. "Sustained release of bupivacaine for post-surgical pain relief using core–shell microspheres". J. Mater. Chem. B 2, n.º 46 (2014): 8194–200. http://dx.doi.org/10.1039/c4tb00948g.

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Dutta, D., C. Fauer, K. Hickey, M. Salifu e S. E. Stabenfeldt. "Tunable delayed controlled release profile from layered polymeric microparticles". Journal of Materials Chemistry B 5, n.º 23 (2017): 4487–98. http://dx.doi.org/10.1039/c7tb00138j.

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Wen, He, Litian Qu, Yu Zhang, Beilei Xu, Shiqi Ling, Xiaochun Liu, Yang Luo, Da Huo, Wei Li e Xu Yao. "A Dendritic Cells-Targeting Nano-Vaccine by Coupling Polylactic-Co-Glycolic Acid-Encapsulated Allergen with Mannan Induces Regulatory T Cells". International Archives of Allergy and Immunology 182, n.º 9 (2021): 777–87. http://dx.doi.org/10.1159/000512872.

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Background: The efficacy of allergen-specific immunotherapy (AIT) is mainly depended on the tolerogenic immune responses elicited. Properly conjugated nano-vaccine has the advantages of both specific targeting and continuous and on-demand release of allergen. Objectives: The aim of this study is to investigate the effects of a dendritic cells (DCs)-targeting nano-vaccine for AIT. Methods: The nano-vaccine was produced by coupling polylactic-co-glycolic acid (PLGA)-encapsulated ovalbumin (OVA) with mannan. Allergen capture, human monocytes-derived DCs (hMoDCs) activation, and T cells responses were assessed by flow cytometry, confocal microscopy, quantitative real-time PCR, ELISA, and Cytometric Bead Array. Balb/c mice were immunized with the nano-vaccines, and the immune responses were analyzed. Results: OVA-PLGA nanoparticle (NP) displayed favorable safety profile. OVA-mannan-PLGA NP was captured more efficiently by hMoDCs than OVA-PLGA NP, which was mediated mainly through DC-specific intercellular adhesion molecule 3-grabbing nonintegrin. A tolerogenic phenotype of hMoDCs was induced by OVA-mannan-PLGA NP, but not OVA-PLGA NP, and increased number of regulatory T (Treg) cells was generated subsequently in in vitro coculture. Immunization of Balb/c mice with OVA-mannan-PLGA NP resulted in lower serum level of OVA-specific immunoglobulins and less production of pro-inflammatory cytokines in splenocytes culture than the mice immunized with OVA-PLAG NP, PLGA NP, or OVA, while the number of splenic Treg cells was higher in OVA-mannan-PLGA group than in other groups. Moreover, preimmunization with OVA-mannan-PLGA NP significantly inhibited the Th2 immune response induced by OVA sensitization. Conclusions: The biocompatible PLGA-encapsulated OVA coupling with mannan has augmented ability for tolerance induction and could be developed as a novel vaccine for AIT.

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He, Xiaoming, Naoki Kawazoe e Guoping Chen. "Preparation of Cylinder-Shaped Porous Sponges of Poly(L-lactic acid), Poly(DL-lactic-co-glycolic acid), and Poly(ε-caprolactone)". BioMed Research International 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/106082.

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Design of mechanical skeletons of biodegradable synthetic polymers such as poly(L-lactic acid) (PLLA), poly(DL-lactic-co-glycolic acid) (PLGA), and poly(ε-caprolactone) (PCL) is important in the construction of the hybrid scaffolds of biodegradable synthetic polymers and naturally derived polymers such as collagen. In this study, cylinder-shaped PLLA, PLGA, and PCL sponges were prepared by the porogen leaching method using a cylinder model. The effects of polymer type, polymer fraction, cylinder height, pore size, and porosity on the mechanical properties of the cylinder-shape sponges were investigated. SEM observation showed that these cylinder-shaped sponges had evenly distributed bulk pore structures and the wall surfaces were less porous with a smaller pore size than the wall bulk pore structures. The porosity and pore size of the sponges could be controlled by the ratio and size of the porogen materials. The PLGA sponges showed superior mechanical properties than those of the PLLA and PCL sponges. Higher porosity resulted in an inferior mechanical strength. The pore size and sponge height also affected the mechanical properties. The results indicate that cylinder-shaped sponges can be tethered by choosing the appropriate polymers, size and ratio of porogen materials and dimension of sponges based on the purpose of the application.

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Niu, Lijing, Chengmin Feng, Chengyi Shen, Bing Wang e Xiaoming Zhang. "PLGA/PLCA casting and PLGA/PDPA electrospinning bilayer film for prevention of postoperative adhesion". Journal of Biomedical Materials Research Part B: Applied Biomaterials 107, n.º 6 (13 de dezembro de 2018): 2030–39. http://dx.doi.org/10.1002/jbm.b.34294.

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Di Gregorio, Enza, Chiara Romiti, Antonino Di Lorenzo, Federica Cavallo, Giuseppe Ferrauto e Laura Conti. "RGD_PLGA Nanoparticles with Docetaxel: A Route for Improving Drug Efficiency and Reducing Toxicity in Breast Cancer Treatment". Cancers 15, n.º 1 (20 de dezembro de 2022): 8. http://dx.doi.org/10.3390/cancers15010008.

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Breast cancer is the leading cause of cancer-related death in women. Although many therapeutic approaches are available, systemic chemotherapy remains the primary choice, especially for triple-negative and advanced breast cancers. Unfortunately, systemic chemotherapy causes serious side effects and requires high doses to achieve an effective concentration in the tumor. Thus, the use of nanosystems for drug delivery may overcome these limitations. Herein, we formulated Poly (lactic-co-glycolic acid) nanoparticles (PLGA-NPs) containing Docetaxel, a fluorescent probe, and a magnetic resonance imaging (MRI) probe. The cyclic RGD tripeptide was linked to the PLGA surface to actively target αvβ3 integrins, which are overexpressed in breast cancer. PLGA-NPs were characterized using dynamic light scattering, fast field-cycling 1H-relaxometry, and 1H-nuclear magnetic resonance. Their therapeutic effects were assessed both in vitro in triple-negative and HER2+ breast cancer cells, and in vivo in murine models. In vivo MRI and inductively coupled plasma mass spectrometry of excised tumors revealed a stronger accumulation of PLGA-NPs in the RGD_PLGA group. Targeted PLGAs have improved therapeutic efficacy and strongly reduced cardiac side effects compared to free Docetaxel. In conclusion, RGD-PLGA is a promising system for breast cancer treatment, with positive outcome in terms of therapeutic efficiency and reduction in side effects.

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Wang, Wei, Miaochen Li, Kun Fang, You Wu, Ning Gu e Chuanlai Shen. "Antigen-specific killer polylactic-co-glycolic acid microspheres selectively deplete antigen-specific T cells in vitro and in vivo (TRAN1P.924)". Journal of Immunology 194, n.º 1_Supplement (1 de maio de 2015): 140.6. http://dx.doi.org/10.4049/jimmunol.194.supp.140.6.

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Abstract The strategy of specifically depleting antigen-specific T cells can potentially be used to treat allograft rejection and autoimmunity because it does not suppress the overall immune systems. In this study, we generated killer polylactic-co-glycolic acid (PLGA) microspheres by covalently coupling H-2Kb-Ig and apoptosis-inducing anti-Fas monoclonal antibody (mAb) onto cell-sized PLGA microspheres. The Kb/OVA257-264-Killer PLGAs resulted in a dramatic reduction in the number of OVA257-264-specific CD8+ T cells in an antigen-specific manner in vitro and in vivo, by using a transgenic OT-1 mice model. The bioluminescence imaging revealed that Killer PLGAs dominantly distributed in lung, liver and gut, and was maintained for up to 48 hours in OT-1 mice and a longer time in OT-1 mice than in C57BL/6 mice. Moreover, the Kb-Killer PLGAs were administered intravenously into bm1 mice (H-2Kbm1) that had previously been grafted with ear skin from C57BL/6 mice (H-2Kb). The killer PLGAs selectively decreased the H-2Kb alloantigen-reactive CD8+ T cells infiltrating into the alloskin graft but not CD4+ T cells, and significantly prolonged allograft survival for 41.5 days without the impairment of host overall immune function. Thus, our data highlight the therapeutic potential of this biocompatible and biodegradable killer effectors for the treatment of allograft rejection and autoimmune disease. Keywords: Allograft rejection, PLGA, H-2Kb-Ig

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Sun, Tao, Junxia Bian, Yangyang Wang, Jian Hu, Xueyan Yun, Eerdunbayaer Chen e Tungalag Dong. "One-Step Synthesis of Poly(L-Lactic Acid)-Based Soft Films with Gas Permselectivity for White Mushrooms (Agaricus bisporus) Preservation". Foods 12, n.º 3 (30 de janeiro de 2023): 586. http://dx.doi.org/10.3390/foods12030586.

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Proper packaging can extend the shelf life and maintain the quality of mushrooms during storage. The purpose of this study is to investigate the preservation of Agaricus bisporus using copolymer-modified poly (L-lactide-co-butylene fumarate) and poly (L-lactide-co-glycolic acid) (PLBF and PLGA) packaging. Shelf life and quality were evaluated over 15 days of storage of Agaricus bisporus at 4 ± 1 °C and 90% relative humidity, including weight loss, browning index (BI), total phenolics (TP), ascorbic acid (AA), malondialdehyde content (MDA), electrolyte leakage rate (EC), and superoxide dismutase (SOD) and catalase (CAT). The results showed that mushrooms packaged in PLBF films exhibited better retention in BI, TP, and AA than those with PLLA, PLGA, or polyethylene (PE) films. They can reduce the rate of weight loss, EC, and MDA, which in turn increases the activity of SOD and CAT. PLBF and PLGA have substantially improved flexibility in comparison with PLLA. They also significantly reduced oxygen (O2) and carbon dioxide (CO2) permeability and changed the gas permeability ratio. These positive effects resulted in the effective restriction of O2 and CO2 in these packages, extending the post-harvest storage period of white mushrooms.

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Park, Ji Hoon, Hwi Ju Kang, Doo Yeon Kwon, Bo Keun Lee, Bong Lee, Ju Woong Jang, Heung Jae Chun, Jae Ho Kim e Moon Suk Kim. "Biodegradable poly(lactide-co-glycolide-co-ε-caprolactone) block copolymers – evaluation as drug carriers for a localized and sustained delivery system". Journal of Materials Chemistry B 3, n.º 41 (2015): 8143–53. http://dx.doi.org/10.1039/c5tb01542a.

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To develop an appropriate drug carrier for drug delivery systems, we prepared random poly(lactide-co-glycolide-co-ε-caprolactone) (PLGC) copolymers in comparison to commercial poly(lactic acid-co-glycolic acid) (PLGA) grades.

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Zhang, Jin, Shu-Gui Yang, Jian-Xun Ding e Zhong-Ming Li. "Tailor-made poly(l-lactide)/poly(lactide-co-glycolide)/hydroxyapatite composite scaffolds prepared via high-pressure compression molding/salt leaching". RSC Advances 6, n.º 53 (2016): 47418–26. http://dx.doi.org/10.1039/c6ra06906a.

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The degradation rate, hydrophilicity, and mechanical properties of PLLA/PLGA/HA scaffolds can be tuned by adjusting the composition. Such tailor-made scaffolds are hopeful to address the specific requirements of the regenerated tissue.

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Nanaki, Stavroula G., Konstantinos Spyrou, Chryssa Bekiari, Pelagia Veneti, Turki N. Baroud, Niki Karouta, Ioannis Grivas, Georgios C. Papadopoulos, Dimitrios Gournis e Dimitrios N. Bikiaris. "Hierarchical Porous Carbon—PLLA and PLGA Hybrid Nanoparticles for Intranasal Delivery of Galantamine for Alzheimer’s Disease Therapy". Pharmaceutics 12, n.º 3 (4 de março de 2020): 227. http://dx.doi.org/10.3390/pharmaceutics12030227.

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In the present study, poly(l-lactic acid) (PLLA) and poly(lactide-co-glycolide) (PLGA) hybrid nanoparticles were developed for intranasal delivery of galantamine, a drug used in severe to moderate cases of Alzheimer’s disease. Galantamine (GAL) was adsorbed first in hierarchical porous carbon (HPC). Formulations were characterized by FT-IR, which showed hydrogen bond formation between GAL and HPC. Furthermore, GAL became amorphous after adsorption, as confirmed by XRD and differential scanning calorimetry (DSC) studies. GAL was quantified to be 21.5% w/w by TGA study. Adsorbed GAL was nanoencapsulated in PLLA and PLGA, and prepared nanoparticles were characterized by several techniques. Their sizes varied between 182 and 394 nm, with an exception that was observed in nanoparticles that were prepared by PLLA and adsorbed GAL that was found to be 1302 nm in size. DSC thermographs showed that GAL was present in its crystalline state in nanoparticles before its adsorption to HPC, while it remained in its amorphous phase after its adsorption in the prepared nanoparticles. It was found that the polymers controlled the release of GAL both when it was encapsulated alone and when it was adsorbed on HPC. Lastly, PLGA hybrid nanoparticles were intranasally-administered in healthy, adult, male Wistar rats. Administration led to successful delivery to the hippocampus, the brain area that is primarily and severely harmed in Alzheimer’s disease, just a few hours after a single dose.

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Wang, Xiaoyan, Yu Zhang, Wei Xue, Hong Wang, Xiaozhong Qiu e Zonghua Liu. "Thermo-sensitive hydrogel PLGA-PEG-PLGA as a vaccine delivery system for intramuscular immunization". Journal of Biomaterials Applications 31, n.º 6 (25 de novembro de 2016): 923–32. http://dx.doi.org/10.1177/0885328216680343.

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In this work, we explored the potential of thermo-sensitive PLGA-PEG-PLGA with sol-gel transition temperature around 32℃ as an intramuscular vaccine delivery system by using ovalbumin as a model antigen. First, in vitro release test showed that the PLGA-PEG-PLGA-deriving hydrogels could release ovalbumin in vitro in a more sustainable way. From fluorescence living imaging, 50–200 mg/mL of PLGA-PEG-PLGA formulations could release antigen in a sustainable manner in vivo, suggesting that the PLGA-PEG-PLGA hydrogel worked as an antigen-depot. Further, the sustainable antigen release from the PLGA-PEG-PLGA hydrogels increased antigen availability in the spleens of the immunized mice. The intramuscular immunization results showed that 50–200 mg/mL of PLGA-PEG-PLGA formulations promoted significantly more potent antigen-specific IgG immune response. In addition, 200 mg/mL of PLGA-PEG-PLGA formulation significantly enhanced the secretion of both Th1 and Th2 cytokines. From in vitro splenocyte proliferation assay, 50–200 mg/mL of PLGA-PEG-PLGA formulations all initiated significantly higher splenocyte activation. These results indicate that the thermo-sensitive and injectable PLGA-PEG-PLGA hydrogels (particularly, 200 mg/mL of PLGA-PEG-PLGA-based hydrogel) own promising potential as an intramuscular vaccine delivery system.

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Ayyoob, Muhammad, e Young Kim. "Effect of Chemical Composition Variant and Oxygen Plasma Treatments on the Wettability of PLGA Thin Films, Synthesized by Direct Copolycondensation". Polymers 10, n.º 10 (12 de outubro de 2018): 1132. http://dx.doi.org/10.3390/polym10101132.

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The synthesis of high molecular weight poly (lactic-co-glycolic) acid (PLGA) copolymers via direct condensation copolymerization is itself a challenging task. Moreover, some of the characteristic properties of polylactide (PLA)-based biomaterials, such as brittleness, hydrophobicity, and longer degradation time, are not suitable for certain biomedical applications. However, such properties can be altered by the copolymerization of PLA with other biodegradable monomers, such as glycolic acid. A series of high molecular weight PLGAs were synthesized through the direct condensation copolymerization of lactic and glycolic acids, starting from 0 to 50 mol% of glycolic acid, and the wettability of its films was monitored as a function of the feed molar ratio. Copolymerization was performed in the presence of a bi-catalytic system using stannous chloride dihydrate and methanesulfonic acid (MSA). The viscosity average molecular weight of the resulting PLGA was in the range of 80k to 135k g/mol. The PLGA films were prepared using the solvent casting technique, and were treated with oxygen plasma for 2 min. The water contact angle of the PLGA films was determined before and after the oxygen plasma treatments, and it was observed that the wettability increased with an increase in the glycolic acid contents, however, the manifolds increased after 2 min of oxygen plasma treatments.

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Gupta, Siddharth, C. Anand Kumar e Namita Raghav. "Polymorphous Low-grade Adenocarcinoma of the Palate: Report of a Case and Review of Literature". International Journal of Head and Neck Surgery 2, n.º 1 (2011): 57–60. http://dx.doi.org/10.5005/jp-journals-10001-1049.

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ABSTRACT Polymorphous low-grade adenocarcinoma (PLGA) is a malignancy arising predominantly from minor salivary glands. PLGAs account for 10% of all tumors and 25% of all malignancies of the minor salivary glands. It has been frequently described as occurring in hard or soft palate minor salivary glands; some cases being described in the tongue and in major salivary glands. We report a case of PLGA of the palate extending into the maxillary sinus and nasal cavity diagnosed on the basis of histopathology and treated by subtotal maxillectomy. The review of literature concerning clinical, histological and immunohistochemical features, as well as the proper management concerning this tumor is included.

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Li, Gang, Dong Hai Lin, Xin Xin Xie, Li Fang Qin e Jun Teng Wang. "Cellular Uptake of PEGylated PLGA Nanoparticles in Hela Cells". Advanced Materials Research 528 (junho de 2012): 80–83. http://dx.doi.org/10.4028/www.scientific.net/amr.528.80.

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PLGA nanoparticles (PLGA-NPs) are being extensively studied as drug carriers for their controlled release, biodegradability and biocompatibility. This study evaluated the cellular uptake of PEGylated PLGA-NPs in Hela cells. MePEG-PLGA (5%-15%) was used to prepare PEG modified PLGA nanoparticles (PEG-PLGA-NPs), and the fluorescent marker DiI was encapsulated in the nanoparticles for the visualized analysis. The nanoparticles were characterized for surface morphology, particle size, zeta potential, and for cellular uptake by Hela cells. Results showed that PLGA nanoparticles were lowly cytotoxic and could be uptaken by Hela cells freely. PEG-PLGA-NPs had faster cellular uptake than that of nude PLGA nanoparticles, especially 10%PEG-PLGA-NPs. It suggested that the surface modification of PLGA-NPs by PEG notably improved the cellular uptake.

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Ha, Hyun Jung, Jeong Eun Song, Yunmi Kang, Eun Young Kim, Sun Jung Yoon, Young Il Yang, Dongwon Lee e Gilson Khang. "PORCINE SMALL INTESTINAL SUBMUCOSA REDUCES THE INFLAMMATORY REACTION OF POLY(LACTIDE-CO-GLYCOLIDE) FILMS". Biomedical Engineering: Applications, Basis and Communications 26, n.º 02 (12 de março de 2014): 1450032. http://dx.doi.org/10.4015/s101623721450032x.

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Poly(lactide-co-glycolide) (PLGA), a well-known synthetic polymer comprised of PLA and PGA, is used commonly as a scaffold for soft and hard tissue engineering purposes; however, the appropriate strategies for reducing its host tissue inflammatory response remain obscure. Porcine small intestinal submucosa (SIS) has been applied as a natural, biodegradable matrix for dressing materials, tendon graft substitutes and scaffolds. We hypothesized that the host tissue reaction of PLGA might occur but could be reduced by impregnating SIS into PLGA. We manufactured PLGA/SIS hybrid films with 0, 10, 20, 40 and 80 wt.% SIS of PLGA. The inflammatory potential of PLGA was evaluated using mRNA expression of TNF-α, IL-1β and IL-6 in the surrounding tissue of implanted scaffolds. The response of subcutaneously implanted PLGA/SIS films were compared to PLGA film; the local inflammatory response was observed by histology. PLGA/SIS films, especially PLGA/SIS films containing 20, 40 and 80 wt.% SIS, elicited a significantly lower expression of IL-1β, TNF-α and IL-6 than PLGA film. PLGA/SIS films demonstrated a favorable tissue response profile compared to PLGA film, with significant less inflammation and fibrous capsule formation as below only 20 wt.% of PLGA/SIS film during implantation. This study demonstrates reduced inflammatory response of PLGA by different amounts of SIS and PLGA/SIS scaffolds being used for tissue engineering constructs.

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Purnavita, Sari, Lucia Hermawati e Elisa Rinihapsari. "Karakteristik Poli Asam Laktat Glikolat (Kajian Rasio Asam Laktat Limbah Aren-Asam Glikolat)". METANA 17, n.º 2 (1 de dezembro de 2021): 88–96. http://dx.doi.org/10.14710/metana.v17i2.36698.

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Polimer Poli Asam Laktat Glikolat (PLGA) merupakan salah satu jenis polimer yang telah disetujui FDA dan EMA untuk penggunaan biomedik. Kelebihan PLGA yaitu biokompatibilitas, biodegradabilitas, fleksibilitas, dan efek samping yang minimal. PLGA telah dikembangkan untuk penggunaan medis namun pemenuhannya masih berupa impor. Oleh karena itu, pada penelitian ini monomer asam laktat dari limbah pati aren dan asam glikolat dengan rasio LA:GA = 75%:25%; 90%:10%; 95%:5%; direaksikan secara Ring Opening Polymerization (ROP) dengan bantuan katalis Sn(II) Oktoat membentuk PLGA. PLGA hasil kemudian ditambahkan PVA, dengan rasio PLGA:PVA 3:2; 3:3; 3:4; dan 3:5 dengan metode solution casting membentuk film. Penelitian dilakukan secara eksperimental dengan Rancangan Acak Lengkap (RAL) faktorial. Hasil penelitian menunjukkan adanya kombinasi rasio LA:GA dan rasio penambahan PVA mempengaruhi karakteristik film PLGA. Hasil kekakuan dan Modulus Young film PLGA tertinggi pada kombinasi penambahan rasio LA:GA = 75%:25% dan penambahan rasio PLGA:PVA =3:4. Biodegrabilitas film PLGA terbaik pada kombinasi penambahan rasio LA:GA 90%:10% dan penambahan rasio PLGA:PVA 3:4. Film PLGA memiliki biokompatibilitas yang baik pada semua rasio LA:GA, dengan penambahan rasio PLGA:PVA lebih dari 3:2. Hasil film PLGA memiliki morfologi permukaan paling halus pada rasio penambahan PLGA : PVA 3:2, dan memiliki struktur semi kristalin.Lactic Glycolic Acid Polymer (PLGA) is a type of polymer that has been approved by the FDA and EMA for biomedical use. The advantages of PLGA are biocompatibility, biodegradability, flexibility, and minimal side effects. PLGA has been developed for medical use but fulfillment is still imported. Therefore, in this study, the lactic acid monomer from waste palm starch and glycolic acid with a ratio of LA: GA = 75%: 25%; 90%: 10%; 95%: 5%; reacted with Ring Opening Polymerization (ROP) with the help of a catalyst Sn (II) Octoate to form PLGA. The resulting PLGA was then added with PVA, with a ratio of PLGA: PVA 3: 2; 3: 3; 3: 4; and 3: 5 with the solution casting method forming the film. This research was conducted experimentally with a factorial completely randomized design (CRD). The results showed that the combination of LA: GA ratio and PVA addition ratio affected the PLGA film characteristics. The results of stiffness and Young's Modulus of PLGA film were highest in the combination of addition of the ratio of LA: GA = 75%: 25% and the addition of the ratio of PLGA: PVA = 3: 4. The best PLGA film biodegradability was combined with the addition of the ratio of LA: GA 90%: 10% and the addition of the PLGA: PVA ratio 3: 4. PLGA film has good biocompatibility in all LA: GA ratios, with the addition of a PLGA: PVA ratio of more than 3: 2. The results of the PLGA film had the smoothest surface morphology at the ratio of addition of PLGA: PVA 3: 2, and had a semi-crystalline structure.

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Maeda, Tomoki, Midori Kitagawa, Atsushi Hotta e Satoshi Koizumi. "Thermo-Responsive Nanocomposite Hydrogels Based on PEG-b-PLGA Diblock Copolymer and Laponite". Polymers 11, n.º 2 (2 de fevereiro de 2019): 250. http://dx.doi.org/10.3390/polym11020250.

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Poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) (PEG-b-PLGA) diblock copolymers are widely known as polymeric surfactants for biomedical applications, and exhibit high solubility in water compared to PLGA-b-PEG-b-PLGA triblock copolymers known as gelation agents. In order to overcome the difficulties in the preparation of thermo-responsive hydrogels based on PLGA-b-PEG-b-PLGA due to the low solubility in water, the fabrication of thermo-responsive hydrogels based on PEG-b-PLGA with high solubility in water was attempted by adding laponite to the PEG-b-PLGA solution. In detail, PEG-b-PLGA with high solubility in water (i.e., high PEG/PLGA ratio) were synthesized. Then, the nanocomposite solution based on PEG-b-PLGA and laponite (laponite/PEG-b-PLGA nanocomposite) was fabricated by mixing the PEG-b-PLGA solutions and the laponite suspensions. By using the test tube inversion method and dynamic mechanical analysis (DMA), it was found that thermo-responsive hydrogels could be obtained by using PEG-b-PLGA, generally known as polymeric surfactants, and that the gelation temperature was around the physiological temperature and could be regulated by changing the solution composition. Furthermore, from the structural analysis by small angle neutron scattering (SANS), PEG-b-PLGA was confirmed to be on the surface of the laponite platelets, and the thermosensitive PEG-b-PLGA on the laponite surface could trigger the thermo-responsive connection of the preformed laponite network.

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Sousa-Batista, Ariane J., Natalia Arruda-Costa, Douglas O. Escrivani, Franceline Reynaud, Patrick G. Steel e Bartira Rossi-Bergmann. "Single-dose treatment for cutaneous leishmaniasis with an easily synthesized chalcone entrapped in polymeric microparticles". Parasitology 147, n.º 9 (4 de maio de 2020): 1032–37. http://dx.doi.org/10.1017/s0031182020000712.

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AbstractCutaneous leishmaniasis (CL) is a major health problem in many countries and its current treatment involves multiple parenteral injections with toxic drugs and requires intensive health services. Previously, the efficacy of a single subcutaneous injection with a slow-release formulation consisting of poly(lactide-co-glycolide) (PLGA) microparticles loaded with an antileishmanial 3-nitro-2-hydroxy-4,6-dimethoxychalcone (CH8) was demonstrated in mice model. In the search for more easily synthesized active chalcone derivatives, and improved microparticle loading, CH8 analogues were synthesized and tested for antileishmanial activity in vitro and in vivo. The 3-nitro-2′,4′,6′-trimethoxychalcone (NAT22) analogue was chosen for its higher selectivity against intracellular amastigotes (selectivity index = 1489, as compared with 317 for CH8) and more efficient synthesis (89% yield, as compared with 18% for CH8). NAT22 was loaded into PLGA / polyvinylpyrrolidone (PVP) polymeric blend microspheres (NAT22-PLGAk) with average diameter of 1.9 μm. Although NAT22-PLGAk showed similar activity to free NAT22 in killing intracellular parasites in vitro (IC50 ~ 0.2 μm), in vivo studies in Leishmania amazonensis – infected mice demonstrated the significant superior efficacy of NAT22-PLGAk to reduce the parasite load. A single intralesional injection with NAT22-PLGAk was more effective than eight injections with free NAT22. Together, these results show that NAT22-PLGAk is a promising alternative for single-dose localized treatment of CL.

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Silva, Marcela Fernandes, Ana Adelina Winkler Hechenleitner, Juan Manuel Irache, Adilson Jesus Aparecido de Oliveira e Edgardo Alfonso Gómez Pineda. "Study of Thermal Degradation of PLGA, PLGA Nanospheres and PLGA/Maghemite Superparamagnetic Nanospheres". Materials Research 18, n.º 6 (24 de novembro de 2015): 1400–1406. http://dx.doi.org/10.1590/1516-1439.045415.

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Zhou, Jinglun, Linlin Li, Weishan Wang, Yang Zhao e Shengyu Feng. "pH-responsive polymeric vesicles from branched copolymers". RSC Advances 9, n.º 70 (2019): 41031–37. http://dx.doi.org/10.1039/c9ra08703f.

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A new type of branched copolymer, poly(l-lactide)₂-b-poly(l-glutamic acid), based on polypeptide PLGA is synthesized by the ring-opening polymerization of N-carboxyanhydride of γ-benzyl-l-glutamate with amino-terminated PLLA₂–NH₂ and subsequent deprotection.

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Lee, Jae Baek, Young-Gwang Ko, Donghwan Cho, Won Ho Park, Byeong Nam Kim, Byeong Cheol Lee, Inn-Kyu Kang e Oh Hyeong Kwon. "Modification of PLGA Nanofibrous Mats by Electron Beam Irradiation for Soft Tissue Regeneration". Journal of Nanomaterials 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/295807.

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Biodegradable poly(lactide-co-glycolide) (PLGA) has found widespread use in modern medical practice. However, the degradation rate of PLGA should be adjusted for specific biomedical applications such as tissue engineering, drug delivery, and surgical implantation. This study focused on the effect of electron beam radiation on nanofibrous PLGA mats in terms of physical properties and degradation behavior with cell proliferation. PLGA nanofiber mats were prepared by electrospinning, and electron beam was irradiated at doses of 50, 100, 150, 200, 250, and 300 kGy. PLGA mats showed dimensional integrity after electron beam irradiation without change of fiber diameter. The degradation behavior of a control PLGA nanofiber (0 kGy) and electron beam-irradiated PLGA nanofibers was analyzed by measuring the molecular weight, weight loss, change of chemical structure, and fibrous morphology. The molecular weight of the PLGA nanofibers decreased with increasing electron beam radiation dose. The mechanical properties of the PLGA nanofibrous mats were decreased with increasing electron beam irradiation dose. Cell proliferation behavior on all electron beam irradiated PLGA mats was similar to the control PLGA mats. Electron beam irradiation of PLGA nanofibrous mats is a potentially useful approach for modulating the biodegradation rate of tissue-specific nonwoven nanofibrous scaffolds, specifically for soft tissue engineering applications.

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Simon, Lacey C., Rhett W. Stout e Cristina Sabliov. "Bioavailability of Orally Delivered Alpha-Tocopherol by Poly(Lactic-Co-Glycolic) Acid (PLGA) Nanoparticles and Chitosan Covered PLGA Nanoparticles in F344 Rats". Nanobiomedicine 3 (1 de janeiro de 2016): 8. http://dx.doi.org/10.5772/63305.

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It is hypothesized that the bioavailability of αT (alpha-tocopherol), an antioxidant, can be improved when delivered by poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) and chitosan covered PLGA nanoparticles (PLGA-Chi NPs), and that the mucoadhesive properties of chitosan may enhance absorption of αT. PLGA and PLGA-Chi NPs were characterized by measuring entrapment efficiency, size, polydispersity, and zeta potential. Nanoparticle physical stability, chemical stability of entrapped αT, and release kinetics were also measured. Pharmacokinetic studies were conducted by administering PLGA (αT) NPs, PLGA-Chi (αT) NPs, and free αT via oral gavage in rats. The size and zeta potential of the two particle systems were 97.87 ± 2.63 nm and −36.2 ± 1.31 mV for PLGA(αT) NPs, and 134 ± 2.05 nm and 38.0 ± 2.90 mV for PLGA-Chi (αT) nanoparticles in DI water. The particle systems showed to be stable during various in vitro assays. Bioavailability of nanodelivered αT was improved compared to the free αT, by 170% and 121% for PLGA and PLGA-Chi NPs, respectively. It was concluded that while chitosan did not further improved bioavailability of αT, PLGA NPs protected the entrapped drug from the GI environment degradation and proved to be an effective delivery system for αT.

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Arizmendi, Narcy, Hui Qian, Yiming Li e Marianna Kulka. "Sesquiterpene-Loaded Co-Polymer Hybrid Nanoparticle Effects on Human Mast Cell Surface Receptor Expression, Granule Contents, and Degranulation". Nanomaterials 11, n.º 4 (8 de abril de 2021): 953. http://dx.doi.org/10.3390/nano11040953.

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Biodegradable polymeric nanoparticles (NPs) such as poly(lactic-co-glycolic acid) (PLGA) and polyvinyl alcohol (PVA) have been used as drug delivery systems for natural and synthetic compounds and are designed to control the loading and release of biodegradable materials to target cells, tissues, and organs. Eremophilane-type sesquiterpenes have anti-inflammatory properties but are lipophilic, cytotoxic, and not biocompatible with many cells. To determine whether biodegradable PLGA/PVA could improve the biocompatibility of sesquiterpenes, sesquiterpene-loaded NPs were synthesized and their effects on human mast cells (LAD2), the major effector cells of allergic inflammation, were determined. NPs composed of PLGA/PVA and two types of sesquiterpenes (fukinone, PLGA/PVA-21 and 10βH-8α,12-epidioxyeremophil-7(11)-en-8β-ol, PLGA/PVA-22) were produced using a microfluidic synthesis method. The NPs’ size distribution and morphology were evaluated by dynamic light scattering and cryogenic transmission electron microscopy (TEM). PLGA/PVA-21 and PLGA/PVA-22 were 60 to 70 nm and were readily internalized by LAD2 as shown by flow cytometry, fluorescence microscopy, and TEM. While unencapsulated sesquiterpenes decreased LAD2 cell viability by 20%, PLGA/PVA-21 and PLGA/PVA-22 did not alter LAD2 viability, showing that encapsulation improved the biocompatibility of the sesquiterpenes. PLGA/PVA-21 and PLGA/PVA-22 decreased the expression of genes encoding the subunits of the high affinity immunoglobulin E receptor (FcεR1α, FcεR1β, FcεR1γ) and the stem cell factor receptor (Kit,), suggesting that hybrid NPs could alter mast cell responses to antigens and shift their maturation. Similarly, PLGA/PVA-21 and PLGA/PVA-22 inhibited tryptase expression but had no effect on chymase expression, thereby promoting a shift to the tryptase-positive phenotype (MCT). Lastly, PLGA/PVA-21 and PLGA/PVA-22 inhibited mast cell degranulation when the LAD2 cells were activated by IgE crosslinking and FcεRI. Overall, our results suggest that PLGA/PVA-21 and PLGA/PVA-22 alter human mast cell phenotype and activation without modifying viability, making them a more biocompatible approach than treating cells with sesquiterpenes alone.

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Mendes Junior, Dario, Juliana A. Domingues, Moema A. Hausen, Silvia M. M. Cattani, Aguedo Aragones, Alexandre L. R. Oliveira, Rodrigo F. Inácio, Maria L. P. Barbo e Eliana A. R. Duek. "Study of Mesenchymal Stem Cells Cultured on a Poly(Lactic-co-Glycolic Acid) Scaffold Containing Simvastatin for Bone Healing". Journal of Applied Biomaterials & Functional Materials 15, n.º 2 (8 de março de 2017): 133–41. http://dx.doi.org/10.5301/jabfm.5000338.

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Background Tissue engineering is a promising alternative for the development of bone substitutes; for this purpose, three things are necessary: stem cells, a scaffold to allow tissue growth and factors that induce tissue regeneration. Methods To congregate such efforts, we used the bioresorbable and biocompatible polymer poly(lactic-co-glycolic acid) (PLGA) as scaffold. For the osteoinductive factor, we used simvastatin (SIM), a drug with a pleiotropic effect on bone growth. Mesenchymal stem cells (MSCs) were cultured in PLGA containing SIM, and the bone substitute of PLGA/SIM/MSC was grafted into critical defects of rat calvaria. Results The in vitro results showed that SIM directly interfered with the proliferation of MSC promoting cell death, while in the pure PLGA scaffold the MSC grew continuously. Scaffolds were implanted in the calvaria of rats and separated into groups: control (empty defect), PLGA pure, PLGA/SIM, PLGA/MSC and PLGA/SIM/MSC. The increase in bone growth was higher in the PLGA/SIM group. Conclusions We observed no improvement in the growth of bone tissue after implantation of the PLGA/SIM/MSC scaffold. As compared with in vitro results, our main hypothesis is that the microarchitecture of PLGA associated with low SIM release would have created an in vivo microenvironment of concentrated SIM that might have induced MSC death. However, our findings indicate that once implanted, both PLGA/SIM and PLGA/MSC contributed to bone formation. We suggest that strategies to maintain the viability of MSCs after cultivation in PLGA/SIM will contribute to improvement of bone regeneration.

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Hsu, Ching Wen, Ping Liu, Song Song Zhu, Feng Deng e Bi Zhang. "Combined Effects of Bone Marrow-Derived Mesenchymal Stem Cells and PLGA-PEG-PLGA Scaffolds on Repair of Articular Cartilage Defect". Advanced Materials Research 815 (outubro de 2013): 345–49. http://dx.doi.org/10.4028/www.scientific.net/amr.815.345.

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Here we reported a combined technique for articular cartilage repair, consisting of bone arrow mesenchymal stem cells (BMMSCs) and poly (dl-lactide-co-glycolide-b-ethylene glycol-b-dl-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers carried with tissue growth factor (TGF-belat1). In the present study, BMMSCs seeded on PLGA-PEG-PLGA with were incubated in vitro, carried or not TGF-belta1, Then the effects of the composite on repair of cartilage defect were evaluated in rabbit knee joints in vivo. Full-thickness cartilage defects (diameter: 5 mm; depth: 3 mm) in the patellar groove were either left empty (n=18), implanted with BMMSCs/PLGA (n=18), TGF-belta1 modified BMMSCs/PLGA-PEG-PLGA. The defect area was examined grossly, histologically at 6, 24 weeks postoperatively. After implantation, the BMMSCs /PLGA-PEG-PLGA with TGF-belta1 group showed successful hyaline-like cartilage regeneration similar to normal cartilage, which was superior to the other groups using gross examination, qualitative and quantitative histology. These findings suggested that a combination of BMMSCs/PLGA-PEG-PLGA carried with tissue growth factor (TGF-belat1) may be an alternative treatment for large osteochondral defects in high loading sites.

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Ajalloueian, Fatemeh, Hossein Tavanai, Jöns Hilborn, Olivier Donzel-Gargand, Klaus Leifer, Abeni Wickham e Ayyoob Arpanaei. "Emulsion Electrospinning as an Approach to Fabricate PLGA/Chitosan Nanofibers for Biomedical Applications". BioMed Research International 2014 (2014): 1–13. http://dx.doi.org/10.1155/2014/475280.

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Novel nanofibers from blends of polylactic-co-glycolic acid (PLGA) and chitosan have been produced through an emulsion electrospinning process. The spinning solution employed polyvinyl alcohol (PVA) as the emulsifier. PVA was extracted from the electrospun nanofibers, resulting in a final scaffold consisting of a blend of PLGA and chitosan. The fraction of chitosan in the final electrospun mat was adjusted from 0 to 33%. Analyses by scanning and transmission electron microscopy show uniform nanofibers with homogenous distribution of PLGA and chitosan in their cross section. Infrared spectroscopy verifies that electrospun mats contain both PLGA and chitosan. Moreover, contact angle measurements show that the electrospun PLGA/chitosan mats are more hydrophilic than electrospun mats of pure PLGA. Tensile strengths of 4.94 MPa and 4.21 MPa for PLGA/chitosan in dry and wet conditions, respectively, illustrate that the polyblend mats of PLGA/chitosan are strong enough for many biomedical applications. Cell culture studies suggest that PLGA/chitosan nanofibers promote fibroblast attachment and proliferation compared to PLGA membranes. It can be assumed that the nanofibrous composite scaffold of PLGA/chitosan could be potentially used for skin tissue reconstruction.

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Nanaki, Stavroula G., Sophia Andrianidou, Panagiotis Barmpalexis, Evi Christodoulou e Dimitrios N. Bikiaris. "Leflunomide Loaded Chitosan Nanoparticles for the Preparation of Aliphatic Polyester Based Skin Patches". Polymers 13, n.º 10 (11 de maio de 2021): 1539. http://dx.doi.org/10.3390/polym13101539.

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In the present study, the preparation of controlled-released leflunomide (LFD)-loaded skin patches was evaluated, utilizing the combination of chitosan (CS) nanoparticles (NPs) incorporated into suitable poly(l-lactic acid) (PLLA) or poly(lactic-co-glycolic acid) (PLGA) polyester matrices. Initially, LFD-loaded CS NPs of ~600 nm and a smooth surface were prepared, while strong inter-molecular interactions between the drug and the CS were unraveled. In the following step, the prepared LFD-loaded CS NPs were incorporated into PLLA or PLGA, and thin-film patches were prepared via spin-coating. Analysis of the prepared films showed that the incorporation of the drug-loaded CS NPs resulted in a significant increase in the drug’s release rate and extent as compared to neat LFD-loaded polyester patches (i.e., prepared without the use of CS NPs). In-depth analysis of the prepared formulations showed that the amorphization of the drug within the matrix and the increased wetting properties of the prepared CS NPs were responsible for the improved thin-film patch characteristics.

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Wang, Siyuan, Xiaobo Feng, Ping Liu, Youxiu Wei e Baojun Xiao. "Blending of PLGA-PEG-PLGA for Improving the Erosion and Drug Release Profile of PCL Microspheres". Current Pharmaceutical Biotechnology 21, n.º 11 (21 de setembro de 2020): 1079–87. http://dx.doi.org/10.2174/1389201021666200101104116.

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Background: PCL has a long history as an industrialized biomaterial for preparing microspheres, but its hydrophobic property and slow degradation rate often cause drug degeneration, quite slow drug release rate and undesirable tri-phasic release profile. Materials and Methods: In this study, we used the blending material of PLGA-PEG-PLGA and PCL to prepare microspheres. The microspheres degradation and drug release behaviors were evaluated through their molecular weight reduction rate, mass loss rate, morphology erosion and drug release profile. The hydrophilic PLGA-PEG-PLGA is expected to improve the degradation and drug release behaviors of PCL microspheres. Results: Microspheres in blending materials exhibited faster erosion rates than pure PCL microspheres, forming holes much quickly on the particle’s surface for the drug to diffuse out. A higher proportion of PLGA-PEG-PLGA caused faster degradation and erosion rates. The blending microspheres showed much faster drug release rates than pure PCL microspheres. Conclusion: With blending of 25wt% PLGA-PEG-PLGA, the release rate of microspheres speeded up significantly, while, with a further increase of PLGA-PEG-PLGA proportion (50%, 75%, 100%), it accelerated a little. The microspheres with PCL/PLGA-PEG-PLGA of 1/1 exhibited a linear-like drug release profile. The results could be a guideline for preparing microspheres based on blending materials to obtain a desirable release.

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TAŞKOR ÖNEL, Gülce. "Synthesis and Characterization of Poly(lactic-co-glycolic acid) Derived with LGlutamic Acid and L-Aspartic Acid". Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi 16, n.º 1 (31 de março de 2023): 155–68. http://dx.doi.org/10.18185/erzifbed.1235522.

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Poly(lactic-co-glycolic acid) (PLGA) is a biocompatible, biodegradable polymer approved by the FDA and EMA, which is the most widely used in the field of health. In this study, PLGA was synthesized primarily from lactide and glycolide by polycondensation and ring-opening polymerization. Then, amino acid derivatives of PLGA were synthesized by the reaction of PLGA and amino acids in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). The polymers synthesized were PLGA, PLGA-L-glutamic acid (PLGA-G), and PLGA-L-aspartic acid (PLGA-A). The chemical structure of these polymers was confirmed by 1H and 13C Nuclear Magnetic Resonance (1H NMR and 13C NMR), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Gel Permeation Chromatography (GPC). When the 13C NMR analyses of PLGA-amino acid derivatives were observed, an increase in the number of carbonyl carbons around 170 ppm was found and the structure accuracy was supported. In addition, when the FTIR analyses of PLGA-amino acid derivatives were examined, the structure was confirmed by observing the signal of the amide bond carbonyl vibration at 1700 cm-1. While the typical endothermic thermogram of the PLGA-amino acid derivative structures was observed by DSC analysis, it was shown that the structures were low molecular weight polymers [~5000-6000 Da] by GPC analysis.

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Yang, Bo, Yongqing Mao, Yanjun Zhang, Yue Hao, Meitong Guo, Bian Li e Haisheng Peng. "HA-Coated PLGA Nanoparticles Loaded with Apigenin for Colon Cancer with High Expression of CD44". Molecules 28, n.º 22 (13 de novembro de 2023): 7565. http://dx.doi.org/10.3390/molecules28227565.

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Apigenin (API) possesses excellent antitumor properties but its limited water solubility and low bioavailability restrict its therapeutic impact. Thus, a suitable delivery system is needed to overcome these limitations and improve the therapeutic efficiency. Poly (lactic-co-glycolic acid) (PLGA) is a copolymer extensively utilized in drug delivery. Hyaluronic acid (HA) is a major extracellular matrix component and can specifically bind to CD44 on colon cancer cells. Herein, we aimed to prepare receptor-selective HA-coated PLGA nanoparticles (HA-PLGA-API-NPs) for colon cancers with high expression of CD44; chitosan (CS) was introduced into the system as an intermediate, simultaneously binding HA and PLGA through electrostatic interaction to facilitate a tighter connection between them. API was encapsulated in PLGA to obtain PLGA-API-NPs, which were then sequentially coated with CS and HA to form HA-PLGA-API-NPs. HA-PLGA-API-NPs had a stronger sustained-release capability. The cellular uptake of HA-PLGA-API-NPs was enhanced in HT-29 cells with high expression of CD44. In vivo, HA-PLGA-API-NPs showed enhanced targeting specificity towards the HT-29 ectopic tumor model in nude mice in comparison with PLGA-API-NPs. Overall, HA-PLGA-API-NPs were an effective drug delivery platform for API in the treatment of colon cancers with high expression of CD44.

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Landau, Shira, Ariel A. Szklanny, Giselle C. Yeo, Yulia Shandalov, Elena Kosobrodova, Anthony S. Weiss e Shulamit Levenberg. "Tropoelastin coated PLLA-PLGA scaffolds promote vascular network formation". Biomaterials 122 (abril de 2017): 72–82. http://dx.doi.org/10.1016/j.biomaterials.2017.01.015.

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Bahcecioglu, Gokhan, Nesrin Hasirci e Vasif Hasirci. "Cell behavior on the alginate-coated PLLA/PLGA scaffolds". International Journal of Biological Macromolecules 124 (março de 2019): 444–50. http://dx.doi.org/10.1016/j.ijbiomac.2018.11.169.

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Albano, Carmen, Gema González, Jordana Palacios, Arquímedes Karam e María Covis. "PLLA-HA vs. PLGA-HA characterization and comparative analysis". Polymer Composites 34, n.º 9 (18 de abril de 2013): 1433–42. http://dx.doi.org/10.1002/pc.22445.

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Xu, Wen, Qingping Zhang e Leiming Sun. "Enhancement of the antitumor effect of cisplatin and ginsenoside Rg3 by encapsulation in polylactic-co-glycolic acid nanoparticles". Tropical Journal of Pharmaceutical Research 23, n.º 1 (5 de fevereiro de 2024): 51–56. http://dx.doi.org/10.4314/tjpr.v23i1.7.

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Purpose: To develop dual-loaded polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) with two chemotherapeutic agents, i.e., cisplatin (DDP) and 20(R)-ginsenoside Rg3(Rg3), and to evaluate the drug release profiles and synergistic inhibitory effects of the nanoparticles on lung cancer A549 cells.Methods: The dual-laden PLGA NPs were synthesized using modified emulsion and solvent vaporization procedures. Drug loading (DL) and efficacy of co-encapsulation (EE) were determined with a modification of column elution technique. The cytotoxic and inhibitory effects of individual and combined drugs on A549 lung cancer cells were evaluated using MTT assay.Results: A sustained pattern of drug release was shown by PLGA/DDP, PLGA/Rg3, and PLGA/DDP+Rg3. The formulated PLGA and unbound drugs exerted dose- and time-reliant cytotoxic effects on A549 cells. At all concentrations tested, drugs encapsulated in PLGA nanoparticles were more effective in killing the cells than the free drugs (p < 0.05). In particular, PLGA/DDP + Rg3 formulation produced a synergistic inhibitory effect on the proliferation of A549 cells.Conclusion: Single- and dual-load PLGA groups display variabilities in profiles of drug release and in vitro cytotoxic effect. Furthermore, dual-load PLGA group produces significantly enhanced treatment effect. These results suggest that PLGA formulations hold great potential for future drug delivery.

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Reich, Karoline M., Petrus Viitanen, Ehsanul Hoque Apu, Stefan Tangl e Nureddin Ashammakhi. "The Effect of Diclofenac Sodium-Loaded Poly(Lactide-co-Glycolide) Rods on Bone Formation and Inflammation: A Histological and Histomorphometric Study in the Femora of Rats". Micromachines 11, n.º 12 (12 de dezembro de 2020): 1098. http://dx.doi.org/10.3390/mi11121098.

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Implants made of poly(lactide-co-glycolide) (PLGA) are biodegradable and frequently provoke foreign body reactions (FBR) in the host tissue. In order to modulate the inflammatory response of the host tissue, PLGA implants can be loaded with anti-inflammatory drugs. The aim of this study was to analyze the impact of PLGA 80/20 rods loaded with the diclofenac sodium (DS) on local tissue reactions in the femur of rats. Special emphasis was put on bone regeneration and the presence of multinucleated giant cells (MGCs) associated with FBR. PLGA 80/20 alone and PLGA 80/20 combined with DS was extruded into rods. PLGA rods loaded with DS (PLGA+DS) were implanted into the femora of 18 rats. Eighteen control rats received unloaded PLGA rods. The follow-up period was of 3, 6 and 12 weeks. Each group comprised of six rats. Peri-implant tissue reactions were histologically and histomorphometrically evaluated. The implantation of PLGA and PLGA+DS8 rods induced the formation of a layer of newly formed bone islands parallel to the contour of the implants. PLGA+DS rods tended to reduce the presence of multi-nucleated giant cells (MGCs) at the implant surface. Although it is known that the systemic administration of DS is associated with compromised bone healing, the local release of DS via PLGA rods did not have negative effects on bone regeneration in the femora of rats throughout 12 weeks.

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Yan, Bohua, Yabing Hua, Jinyue Wang, Tianjiao Shao, Shan Wang, Xiang Gao e Jing Gao. "Surface Modification Progress for PLGA-Based Cell Scaffolds". Polymers 16, n.º 1 (4 de janeiro de 2024): 165. http://dx.doi.org/10.3390/polym16010165.

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Poly(lactic-glycolic acid) (PLGA) is a biocompatible bio-scaffold material, but its own hydrophobic and electrically neutral surface limits its application as a cell scaffold. Polymer materials, mimics ECM materials, and organic material have often been used as coating materials for PLGA cell scaffolds to improve the poor cell adhesion of PLGA and enhance tissue adaptation. These coating materials can be modified on the PLGA surface via simple physical or chemical methods, and coating multiple materials can simultaneously confer different functions to the PLGA scaffold; not only does this ensure stronger cell adhesion but it also modulates cell behavior and function. This approach to coating could facilitate the production of more PLGA-based cell scaffolds. This review focuses on the PLGA surface-modified materials, methods, and applications, and will provide guidance for PLGA surface modification.

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Deng, Duanji, e Honghui Luo. "Effects of Ultrasound Contrast Agent-Encapsulated Paclitaxel Extract on the Proliferation and Invasion Ability of Hepatocellular Carcinoma Cells". Science of Advanced Materials 15, n.º 11 (1 de novembro de 2023): 1496–506. http://dx.doi.org/10.1166/sam.2023.4552.

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Regarding to the limitations of paclitaxel (PTX) in cancer treatment, PTX was extracted from Taxus chinensis and PTX nano-ultrasound contrast agents (NUCA) were prepared to investigate their impacts on proliferation and invasion of hepatocellular carcinoma (HCC) cells (HCCCs). The PTX extract was obtained through extraction and multi-step purification methods using Taxus chinensis as the source material and poly(lactic-co-glycolic acid)-carboxylic acid (PLGA-COOH) as the experimental material. A modified double emulsion solvent evaporation (DESE) method was employed to prepare paclitaxel-loaded PLGA NUCA (PLGA@PTX). The particle size distribution (PSD) and zeta potential (ZP) of PLGA@PTX were identified using a laser particle size (PS) analyzer, while the drug-loading capacity (DLC) and encapsulation efficiency (EE) of PTX in PLGA@PTX NUCA were evaluated using high-performance liquid chromatography (HPLC). The in vitro release rate (IVRR) of PTX from PLGA@PTX NUCA was also analyzed. HepG2 lines, a human HCC cell line, were grouped into four randomly: a blank control group (Blank), a PTX group, a blank nano-contrast agent group without PTX encapsulation (PLGA), and a PTX-loaded NUCA group (PLGA@PTX). In the Blank group, HepG2 lines were cultured conventionally for 12 hours, while PTX or PLGA@PTX was added to the PTX and PLGA@PTX groups, respectively, to achieve a required concentration (10−7 mol/L) of PTX. An equal amount of PLGA nanoparticles was added to the PLGA group. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell were utilized to judge the impacts of PLGA@PTX nanoparticles on proliferation and invasion of HepG2 lines, respectively. Moreover, flow cytometry (FCT) was utilized to examine the influence of PLGA@PTX nanoparticles on cell cycle (CC) and apoptosis of HepG2 lines. The results revealed that the purity of the PTX extract was as high as 99.04±0.92%. The average PS of PLGA@PTX NUCA was (432.79±4.56) nm, with a surface potential of (−10.79±2.28) mV. Furthermore, the EE and DLC were (89.27±2.63) % and (9.03±0.29) %, respectively. The inhibition rate (IR) to HepG2 lines and cell invasion and the apoptotic rate (AR) in the PLGA@PTX group were much higher to those in the PLGA and PTX groups (P <0.01, P <0.05). The ratio of G1/G0 phase in the CC was greatly lower in the PLGA@PTX group to the PLGA and PTX groups, showing obvious differences with (P <0.05), while that of G2/M phase was higher (P <0.05). These findings indicated that the prepared PLGA@PTX NUCA hindered the proliferation and invasion of HepG2 lines and induced CC arrest at the G2/M phase and apoptosis.

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Alshehri, Sultan, Syed Sarim Imam, Md Rizwanullah, Khalid Umar Fakhri, Mohd Moshahid Alam Rizvi, Wael Mahdi e Mohsin Kazi. "Effect of Chitosan Coating on PLGA Nanoparticles for Oral Delivery of Thymoquinone: In Vitro, Ex Vivo, and Cancer Cell Line Assessments". Coatings 11, n.º 1 (23 de dezembro de 2020): 6. http://dx.doi.org/10.3390/coatings11010006.

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In the present study, thymoquinone (TQ)-encapsulated chitosan- (CS)-coated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were formulated using the emulsion evaporation method. NPs were optimized by using 33-QbD approach for improved efficacy against breast cancer. The optimized thymoquinone loaded chitosan coated Poly (d,l-lactide-co-glycolide) nanoparticles (TQ-CS-PLGA-NPs) were successfully characterized by different in vitro and ex vivo experiments as well as evaluated for cytotoxicity in MDA-MB-231 and MCF-7 cell lines. The surface coating of PLGA-NPs was completed by CS coating and there were no significant changes in particle size and entrapment efficiency (EE) observed. The developed TQ-CS-PLGA-NPs showed particle size, polydispersibility index (PDI), and %EE in the range between 126.03–196.71 nm, 0.118–0.205, and 62.75%–92.17%. The high and prolonged TQ release rate was achieved from TQ-PLGA-NPs and TQ-CS-PLGA-NPs. The optimized TQ-CS-PLGA-NPs showed significantly higher mucoadhesion and intestinal permeation compared to uncoated TQ-PLGA-NPs and TQ suspension. Furthermore, TQ-CS-PLGA-NPs showed statistically enhanced antioxidant potential and cytotoxicity against MDA-MB-231 and MCF-7 cells compared to uncoated TQ-PLGA-NPs and pure TQ. On the basis of the above findings, it may be stated that chitosan-coated TQ-PLGA-NPs represent a great potential for breast cancer management.

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Liu, Min, Yiting Liu, Xiaodong Sun e Ting Kang. "Mechanism of poly(lactic acid-glycolic acid) (PLGA) copolymer nanoparticles in enhancing cytotoxicity against occurrence and development of lung cancer metastasis". Materials Express 12, n.º 2 (1 de fevereiro de 2022): 227–33. http://dx.doi.org/10.1166/mex.2022.2159.

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Poly lactic acid-glycolic acid copolymer (PLGA) plays a critical role in inducing tumor cells apoptosis. However, the solubility of the compound itself puts a limit on its use value in treatment of tumor. In this study, we used PLGA combined with nanoparticles as a strategy for metastatic tumor of lung cancer. We evaluated the biological effect of PLGA nanoparticles on enhancing cytotoxicity and its anti-tumor effect against metastasis tumor of lung cancer. Confocal microscope was used to detect the transfection efficiency of tumor cells. PLGA and PLGA-cored nanoparticles (PLGA AC-NPs) were used to interfere with proliferation and apoptosis of metastatic tumor cell line from lung cancer and flow cytometry was used to explore its effect. Furthermore, PLGA and PLGA AC-NPs were injected into the chest of lung cancer mice for treatment. Cell proliferation and apoptosis were detected through measurement of tumor volume, immunohistochemistry (IHC) and Westernblot protein analysis. It was found that, PLGA AC-NPs significantly enhanced cell uptake while PLGA ACNPs regulated tumor by inhibiting cell proliferation and promoting apoptosis. It was also observed in vivo transplanted tumor model that the growth of metastatic tumor of lung cancer was inhibited significantly by NGO-PEG-PEI/Cer, while proliferation and accelerated apoptosis were also slowed down. PLGA AC-NPs can inhibit tumor growth by promoting apoptosis and inhibiting further proliferation of tumor cells.

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Fu, Kai, Yifei Zhou, Jia Hou, Tao Shi, Jie Ni, Xue Li e Hong Zhang. "Floating poly(lactic-co-glycolic acid)-based controlled-release drug delivery system for intravesical instillation". Journal of International Medical Research 51, n.º 4 (abril de 2023): 030006052311620. http://dx.doi.org/10.1177/03000605231162065.

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Objectives To investigate the floating, structural, and controlled-release characteristics of a floating poly(lactic-co-glycolic acid) (PLGA)-based controlled-release drug delivery system, and determine the feasibility of this drug delivery system for intravesical instillation. Methods PLGA was dissolved in dimethylacetamide, then mixed with IR780 and doxorubicin (DOX) to prepare a drug delivery system capable of solidification and flotation on water at room temperature. Preparations of PLGA, PLGA+IR780, PLGA+DOX, and PLGA+IR780+DOX were formulated. Their floating characteristics in vivo and in vitro were investigated, along with their structural and controlled-release characteristics. Preparations of saline, DOX, and PLGA+IR780+DOX were also formulated; the content of DOX in bladder tissue delivered by each preparation was determined by fluorescence microscopy. Results PLGA exhibited stable flotation in vivo and in vitro. A honeycomb structure was observed by scanning electron microscopy. When irradiated with a near-infrared laser, IR780 generated heat that vitrified PLGA, allowing controlled release of DOX from the drug delivery system. The PLGA+IR780+DOX preparation achieved the highest content of DOX in bladder tissue. Conclusions Our floating PLGA-based controlled-release drug delivery system exhibited a honeycomb stabilized structure and achieved controlled release when irradiated by a near-infrared laser, making it an ideal drug delivery system for intravesical instillation.

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Hlaing, Shwe Phyu, Jiafu Cao, Juho Lee, Jihyun Kim, Aruzhan Saparbayeva, Dongmin Kwak, Hyunwoo Kim et al. "Hyaluronic Acid-Conjugated PLGA Nanoparticles Alleviate Ulcerative Colitis via CD44-Mediated Dual Targeting to Inflamed Colitis Tissue and Macrophages". Pharmaceutics 14, n.º 10 (5 de outubro de 2022): 2118. http://dx.doi.org/10.3390/pharmaceutics14102118.

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Although various local anti-inflammatory therapies for ulcerative colitis have been developed, rapid drug elimination from inflamed colitis tissue and off-target side effects reduce their therapeutic efficacy. In this study, we synthesized curcumin (Cur)-loaded hyaluronic acid (HA)-conjugated nanoparticles (Cur-HA-PLGA-NPs) that target inflamed colitis tissue via HA-CD44 interaction with resident colonic epithelial cells and subsequently target activated macrophages for ulcerative colitis therapy. The synthesized spherical Cur-HA-PLGA-NPs showed physicochemical properties similar to those of non-HA-conjugated Cur-PLGA-NPs. HA-PLGA-NPs exhibited selective accumulation in inflamed colitis tissue with minimal accumulation in healthy colon tissue. HA functionalization enhanced targeted drug delivery to intestinal macrophages, significantly increasing HA-PLGA-NP cellular uptake. Importantly, the rectal administration of Cur-HA-PLGA-NPs exhibited better therapeutic efficacy than Cur-PLGA-NPs in animal studies. Histological examination revealed that Cur-HA-PLGA-NPs reduced inflammation with less inflammatory cell infiltration and accelerated recovery with re-epithelialization signs. Our results suggest that Cur-HA-PLGA-NPs are a promising delivery platform for treating ulcerative colitis.

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Сапельников, Максим Дмитриевич, Елена Дмитриевна Никольская, Наталья Борисовна Морозова, Екатерина Александровна Плотникова, Андрей Александрович Панкратов, Анастасия Владимировна Ефременко, Алексей Валерьевич Панов, Михаил Александрович Грин e Раиса Ивановна Якубовская. "Физико-химические и биологические свойства наноструктурированного ИК-фотосенсибилизатора на основе дипропоксибактериопурпуринимида". Химико-фармацевтический журнал 54, n.º 1 (7 de março de 2020): 22–30. http://dx.doi.org/10.30906/0023-1134-2020-54-1-22-30.

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Описан процесс оптимизации технологии получения наночастиц на основе сополимера молочной и гликолевой кислот (PLGA), содержащих дипропоксибактериопурпуринимид (DPBPI) и предназначенных для фотодинамической терапии злокачественных новообразований различного генеза. Предложен подход к снижению среднего диаметра получаемых наночастиц. Получен образец наночастиц DPBPI-PLGA со средним диаметром (142,3 ± 2,7) нм; ξ-потенциалом – (17,1 ± 3,42) мВ; индексом полидисперсности 0,095; общее содержание DPBPI в частицах DPBPI-PLGA — 17,4 мг/г. Осуществлена наработка наночастиц DPBPI-PLGA для биологических исследований. В экспериментах in vitro на клетках А549 изучено внутриклеточное распределение DPBPI в составе наночастиц DPBPI-PLGA. Также изучена кинетика накопления DPBPI в клетках и кинетика его элиминации. Показан высокий уровень фотоиндуцированной цитотоксичности DPBPI-PLGA в экспериментах in vitro. В экспериментах in vivo на модели саркомы мягких тканей мыши S37 показана противоопухолевая активность наночастиц DPBPI-PLGA.

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