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Ye, Jun, Yue Gao, Ming Ji, Yanfang Yang, Zhaohui Wang, Baolian Wang, Jing Jin, et al. "Oral SMEDDS promotes lymphatic transport and mesenteric lymph nodes target of chlorogenic acid for effective T-cell antitumor immunity." Journal for ImmunoTherapy of Cancer 9, no. 7 (July 2021): e002753. http://dx.doi.org/10.1136/jitc-2021-002753.
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BackgroundMesenteric lymph nodes (MLNs) are critical draining lymph nodes of the immune system that accommodate more than half of the body’s lymphocytes, suggesting their potential value as a cancer immunotherapy target. Therefore, efficient delivery of immunomodulators to the MLNs holds great potential for activating immune responses and enhancing the efficacy of antitumor immunotherapy. Self-microemulsifying drug delivery systems (SMEDDS) have attracted increasing attention to improving oral bioavailability by taking advantage of the intestinal lymphatic transport pathway. Relatively little focus has been given to the lymphatic transport advantage of SMEDDS for efficient immunomodulators delivery to the MLNs. In the present study, we aimed to change the intestinal lymphatic transport paradigm from increasing bioavailability to delivering high concentrations of immunomodulators to the MLNs.MethodsChlorogenic acid (CHA)-encapsulated SMEDDS (CHA-SME) were developed for targeted delivery of CHA to the MLNs. The intestinal lymphatic transport, immunoregulatory effects on immune cells, and overall antitumor immune efficacy of CHA-SME were investigated through in vitro and in vivo experiments.ResultsCHA-SME enhanced drug permeation through intestinal epithelial cells and promoted drug accumulation within the MLNs via the lymphatic transport pathway. Furthermore, CHA-SME inhibited tumor growth in subcutaneous and orthotopic glioma models by promoting dendritic cell maturation, priming the naive T cells into effector T cells, and inhibiting the immunosuppressive component. Notably, CHA-SME induced a long-term immune memory effect for immunotherapy.ConclusionsThese findings indicate that CHA-SME have great potential to enhance the immunotherapeutic efficacy of CHA by activating antitumor immune responses.
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Jang, Ji-Hun, Seung-Hyun Jeong, and Yong-Bok Lee. "Preparation and In Vitro/In Vivo Characterization of Polymeric Nanoparticles Containing Methotrexate to Improve Lymphatic Delivery." International Journal of Molecular Sciences 20, no. 13 (July 5, 2019): 3312. http://dx.doi.org/10.3390/ijms20133312.
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Methotrexate (MTX) is a folic acid antagonist used as an effective drug to treat various kinds of cancers. However, MTX has limited use in cancer chemotherapy due to its adverse effects such as poor bioavailability, low specificity, drug resistance, and dose-dependent side effects. To improve lymphatic delivery and reduce toxicity of MTX, MTX-loaded nanoparticles (NPs) were prepared in the present study. NPs were prepared with double emulsion solvent evaporation method using poly(lactide-co-glycolide) (PLGA). NPs were assessed for size, encapsulation efficiency, morphology, Fourier-transform infrared spectroscopy, X-ray diffraction, and thermal characterization. In vitro release profiles and cytotoxicity of these NPs were also evaluated. Prepared NPs and free MTX were administered orally or intravenously (5 mg/kg as MTX) to rats to evaluate their pharmacokinetic characteristics and lymphatic delivery effects. Mean particle size and encapsulation efficiency of NPs were 163.7 ± 10.25 nm and 93.3 ± 0.5%, respectively. Prepared NPs showed a sustained release profile of MTX in vitro and may be effective to cancer cells. Area under the blood concentration-time curve, total clearance, half-life, and lymphatic targeting efficiency were significantly different (p < 0.05) between prepared NPs and free MTX. These results demonstrate that MTX-loaded PLGA NPs are good candidates for targeted delivery of MTX to the lymphatic system.
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Kadian, Renu, and Arun Nanda. "A Comprehensive Insight on Self Emulsifying Drug Delivery Systems." Recent Advances in Drug Delivery and Formulation 16, no. 1 (April 2022): 15–43. http://dx.doi.org/10.2174/2667387815666211207112803.
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Background: The oral route is a highly recommended route for the delivery of a drug. But most lipophilic drugs are difficult to deliver via this route due to their low aqueous solubility. Selfemulsifying drug delivery systems (SEDDS) have emerged as a potential approach of increasing dissolution of a hydrophobic drug due to spontaneous dispersion in micron or nano sized globules in the GI tract under mild agitation. Objective: The main motive of this review article is to describe the mechanisms, advantages, disadvantages, factors affecting, effects of excipients, possible mechanisms of enhancing bioavailability, and evaluation of self-emulsifying drug delivery systems. Result: Self emulsifying systems incorporate the hydrophobic drug inside the oil globules, and a monolayer is formed by surfactants to provide the low interfacial tension, which leads to improvement in the dissolution rate of hydrophobic drugs. The globule size of self-emulsifying systems depends upon the type and ratio of excipients in which they are used. The ternary phase diagram is constructed to find out the range of concentration of excipients used. This review article also presents recent and updated patents on self-emulsifying drug delivery systems. Self-emulsifying systems have the ability to enhance the oral bioavailability and solubility of lipophilic drugs. Conclusion: This technique offers further advantages such as bypassing the first pass metabolism via absorption of drugs through the lymphatic system, easy manufacturing, reducing enzymatic hydrolysis, inter and intra subject variability, and food effects.
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Agrawal, Shivanshu, Anuj Garg, and Vikas Varshney. "Recent Updates On Applications of Lipid-Based Nanoparticles For Site- Specific Drug Delivery." Pharmaceutical Nanotechnology 10, no. 1 (February 2022): 24–41. http://dx.doi.org/10.2174/2211738510666220304111848.
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Background: Site-specific drug delivery is a widespread and demanding area nowadays. Lipid-based nanoparticulate drug delivery systems have shown promising effects for targeting drugs among lymphatic systems, brain tissues, lungs, and skin. Recently, lipid nanoparticles are used for targeting the brain via the mucosal route for local therapeutic effects. Lipid nanoparticles (LNPs) can help in enhancing the efficacy and lowering the toxicities of anticancer drugs to treat the tumors, particularly in lymph after metastases of tumors. LNPs contain a non-polar core that can improve the absorption of lipophilic drugs into the lymph node and treat tumors. Cellular uptake of drugs can also be enhanced using LNPs and therefore, LNPs are the ideal carrier for treating intracellular infections such as leishmaniasis, tuberculosis and parasitic infection in the brain, etc. Furthermore, specific surface modifications with molecules like mannose, or PEG could improve the macrophage uptake and hence effectively eradicate parasites hiding in macrophages. Method: An electronic literature search was conducted to update the advancements in the field of site-specific drug delivery utilizing lipid-based nanoparticles. A search of the Scopus database (https://www.scopus.com/home.uri) was conducted using the following keywords: lipid-based nanoparticles; site specific delivery. Conclusion: Solid lipid nanoparticles have shown site-specific targeted delivery to various organs including the liver, oral mucosa, brain, epidermis, pulmonary and lymphatic systems. These lipid-based systems showed improved bioavailability as well as reduced side effects. Therefore, the focus of this article is to review the recent research studies on LNPs for site-specific or targeting drug delivery.
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Cribb, Matthew T., Lauren F. Sestito, Stanley G. Rockson, Mark R. Nicolls, Susan N. Thomas, and J. Brandon Dixon. "The Kinetics of Lymphatic Dysfunction and Leukocyte Expansion in the Draining Lymph Node during LTB4 Antagonism in a Mouse Model of Lymphedema." International Journal of Molecular Sciences 22, no. 9 (April 24, 2021): 4455. http://dx.doi.org/10.3390/ijms22094455.
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The mechanisms of lymphedema development are not well understood, but emerging evidence highlights the crucial role the immune system plays in driving its progression. It is well known that lymphatic function deteriorates as lymphedema progresses; however, the connection between this progressive loss of function and the immune-driven changes that characterize the disease has not been well established. In this study, we assess changes in leukocyte populations in lymph nodes within the lymphatic drainage basin of the tissue injury site (draining lymph nodes, dLNs) using a mouse tail model of lymphedema in which a pair of draining collecting vessels are left intact. We additionally quantify lymphatic pump function using established near infrared (NIR) lymphatic imaging methods and lymph-draining nanoparticles (NPs) synthesized and employed by our team for lymphatic tissue drug delivery applications to measure lymphatic transport to and resulting NP accumulation within dLNs associated with swelling following surgery. When applied to assess the effects of the anti-inflammatory drug bestatin, which has been previously shown to be a possible treatment for lymphedema, we find lymph-draining NP accumulation within dLNs and lymphatic function to increase as lymphedema progresses, but no significant effect on leukocyte populations in dLNs or tail swelling. These results suggest that ameliorating this loss of lymphatic function is not sufficient to reverse swelling in this surgically induced disease model that better recapitulates the extent of lymphatic injury seen in human lymphedema. It also suggests that loss of lymphatic function during lymphedema may be driven by immune-mediated mechanisms coordinated in dLNs. Our work indicates that addressing both lymphatic vessel dysfunction and immune cell expansion within dLNs may be required to prevent or reverse lymphedema when partial lymphatic function is sustained.
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Király, Gábor, John Chinonso Egu, Zoltán Hargitai, Ilona Kovács, István Fábián, József Kalmár, and Gábor Szemán-Nagy. "Mesoporous Aerogel Microparticles Injected into the Abdominal Cavity of Mice Accumulate in Parathymic Lymph Nodes." International Journal of Molecular Sciences 22, no. 18 (September 9, 2021): 9756. http://dx.doi.org/10.3390/ijms22189756.
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Mesoporous aerogel microparticles are promising drug delivery systems. However, their in vivo biodistribution pathways and health effects are unknown. Suspensions of fluorescein-labeled silica–gelatin hybrid aerogel microparticles were injected into the peritoneum (abdominal cavity) of healthy mice in concentrations of 52 and 104 mg kg−1 in a 3-week-long acute toxicity experiment. No physiological dysfunctions were detected, and all mice were healthy. An autopsy revealed that the aerogel microparticles were not present at the site of injection in the abdominal cavity at the end of the experiment. The histological study of the liver, spleen, kidneys, thymus and lymphatic tissues showed no signs of toxicity. The localization of the aerogel microparticles in the organs was studied by fluorescence microscopy. Aerogel microparticles were not detected in any of the abdominal organs, but they were clearly visible in the cortical part of the parathymic lymph nodes, where they accumulated. The accumulation of aerogel microparticles in parathymic lymph nodes in combination with their absence in the reticuloendothelial system organs, such as the liver or spleen, suggests that the microparticles entered the lymphatic circulation. This biodistribution pathway could be exploited to design passive targeting drug delivery systems for flooding metastatic pathways of abdominal cancers that spread via the lymphatic circulation.
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White, D. G., M. J. Story, and S. G. Barnwell. "An experimental animal model for studying the effects of a novel lymphatic drug delivery system for propranolol." International Journal of Pharmaceutics 69, no. 2 (March 1991): 169–74. http://dx.doi.org/10.1016/0378-5173(91)90221-9.
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Lala, Rita R., Amol S. Shinde, and Nikita Y. Nandvikar. "SOLID LIPID NANOPARTICLES: A PROMISING APPROACH FOR COMBINATIONAL DRUG THERAPY IN CANCER." International Journal of Applied Pharmaceutics 10, no. 5 (September 8, 2018): 17. http://dx.doi.org/10.22159/ijap.2018v10i5.27894.
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Combination therapy for cancer treatment is accepted worldwide due to the generation of synergistic anticancer effects; restrain in multidrug resistance (MDR) or tumor resistance by different mechanisms of action and minimization of dose-dependent toxicity. Recently developed Solid lipid nanoparticles (SLNs) are matrix composed of lipid which is solid at both room and body temperature and hence it is as an alternative to other nanocarrier systems. SLNs after oral administration get absorbed by lymphatic pathway due to stimulation of chylomicron formation. Thus, it avoids all consequences related to an oral drug delivery system and improves oral bioavailability. SLNs based combination drug delivery to tumor tissues reduces the problems associated with chemotherapy. The targeted and sustained delivery of chemotherapeutic agents reduces the dose by achieving high concentrations at the target site, without altering the normal tissues. In this article, we have reviewed and focused on SLNs as a drug delivery system; ingredients used in formulating SLNs and developed two or more drugs in a single formulation of SLNs as drug delivery. This article also focuses on the fact that SLNs as a combination drug delivery provides an attractive approach in future prevention and beneficial for the treatment of cancer by increasing its therapeutic efficacy.
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Gausuzzaman, Syed Abul Layes, Mithun Saha, Shahid Jaman Dip, Shaiful Alam, Arup Kumar, Harinarayan Das, Shazid Md Sharker, Md Abdur Rashid, Mohsin Kazi, and Hasan Mahmud Reza. "A QbD Approach to Design and to Optimize the Self-Emulsifying Resveratrol–Phospholipid Complex to Enhance Drug Bioavailability through Lymphatic Transport." Polymers 14, no. 15 (August 8, 2022): 3220. http://dx.doi.org/10.3390/polym14153220.
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Objectives: Despite having profound therapeutic value, the clinical application of resveratrol is restrained due to its <1% bioavailability, arising from the extensive fast-pass effect along with enterohepatic recirculation. This study aimed to develop a self-emulsifying formulation capable of increasing the bioavailability of resveratrol via lymphatic transport. Methods: The resveratrol–phospholipid complex (RPC) was formed by the solvent evaporation method and characterized by FTIR, DSC, and XRD analyses. The RPC-loaded self-emulsifying drug delivery system (SEDDS) was designed, developed, and optimized using the QbD approach with an emphasis on resveratrol transport through the intestinal lymphatic pathway. The in vivo pharmacokinetic study was investigated in male Wister Albino rats. Results: The FTIR, DSC, and XRD analyses confirmed the RPC formation. The obtained design space provided robustness of prediction within the 95% prediction interval to meet the CQA specifications. An optimal formulation (desirability value of 7.24) provided Grade-A self-emulsion and exhibited a 48-fold bioavailability enhancement compared to the pure resveratrol. The cycloheximide-induced chylomicron flow blocking approach demonstrated that 91.14% of the systemically available resveratrol was transported through the intestinal lymphatic route. Conclusions: This study suggests that an optimal self-emulsifying formulation can significantly increase the bioavailability of resveratrol through lymphatic transport to achieve the desired pharmacological effects.
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Amri, Nada, Rémi Bégin, Nolwenn Tessier, Laurent Vachon, Louis Villeneuve, Philippe Bégin, Renée Bazin, Lionel Loubaki, and Catherine Martel. "Use of Early Donated COVID-19 Convalescent Plasma Is Optimal to Preserve the Integrity of Lymphatic Endothelial Cells." Pharmaceuticals 15, no. 3 (March 17, 2022): 365. http://dx.doi.org/10.3390/ph15030365.
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Convalescent plasma therapy (CPT) has gained significant attention since the onset of the coronavirus disease 2019 (COVID-19) pandemic. However, clinical trials designed to study the efficacy of CPT based on antibody concentrations were inconclusive. Lymphatic transport is at the interplay between the immune response and the resolution of inflammation from peripheral tissues, including the artery wall. As vascular complications are a key pathogenic mechanism in COVID-19, leading to inflammation and multiple organ failure, we believe that sustaining lymphatic vessel function should be considered to define optimal CPT. We herein sought to determine what specific COVID-19 convalescent plasma (CCP) characteristics should be considered to limit inflammation-driven lymphatic endothelial cells (LEC) dysfunction. CCP donated 16 to 100 days after the last day of symptoms was characterized and incubated on inflammation-elicited adult human dermal LEC (aHDLEC). Plasma analysis revealed that late donation correlates with higher concentration of circulating pro-inflammatory cytokines. Conversely, extracellular vesicles (EVs) derived from LEC are more abundant in early donated plasma (r = −0.413, p = 0.004). Thus, secretion of LEC-EVs by an impaired endothelium could be an alarm signal that instigate the self-defense of peripheral lymphatic vessels against an excessive inflammation. Indeed, in vitro experiments suggest that CCP obtained rapidly following the onset of symptoms does not damage the aHDLEC junctions as much as late-donated plasma. We identified a particular signature of CCP that would counteract the effects of an excessive inflammation on the lymphatic endothelium. Accordingly, an easy and efficient selection of convalescent plasma based on time of donation would be essential to promote the preservation of the lymphatic and immune system of infected patients.
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Subramanian, S., P. K. Das, W. Souza, T. Lapa, A. F. Furtado, C. P. B. Van der Ploeg, J. D. F. Habbema, G. J. van Oortmarssen, and A. P. Plaisier. "The LYMFASIM Simulation Program for Modeling Lymphatic Filariasis and its Control." Methods of Information in Medicine 37, no. 01 (1998): 97–108. http://dx.doi.org/10.1055/s-0038-1634505.
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Abstract:The LYMFASIM modeling framework for the transmission and control of the tropical parasitic disease lymphatic filariasis is described and its use in the context of an endemic community in north-eastern Brazil is illustrated. Lymphatic filariasis is a disease with a complex natural history with many unknowns. This complicates decision making with respect to control strategies. With LYMFASIM, a variety of hypotheses can be tested about the life history of the parasite Wuchereria bancrofti, its transmission from man to man through mosquitoes, the role of the immune system in regulating parasite numbers, the development of disease symptoms, and the effects of control measures (drug treatment or mosquito control). The implications of alternative assumptions and uncertainty about the quantification of parameters for the effectiveness of control strategies can be investigated. Thanks to the use of stochastic microsimulation, LYMFASIM is highly flexible and can be adapted and extended as new knowledge emerges.
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Prangsaengtong, Orawin, Phatcharida Jantaree, Kriengsak Lirdprapamongkol, Lukana Ngiwsara, Jisnuson Svasti, and Keiichi Koizumi. "Aspirin suppresses components of lymphangiogenesis and lymphatic vessel remodeling by inhibiting the NF-κB/VCAM-1 pathway in human lymphatic endothelial cells." Vascular Medicine 23, no. 3 (April 9, 2018): 201–11. http://dx.doi.org/10.1177/1358863x18760718.
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Lymphangiogenesis is the process of new vessel formation from pre-existing lymphatic vessels. The process mainly involves cell adhesion, migration, and tubule formation of lymphatic endothelial cells. Tumor-induced lymphangiogenesis is an important factor contributing to promotion of tumor growth and cancer metastasis via the lymphatic system. Finding the non-toxic agents that can prevent or inhibit lymphangiogenesis may lead to blocking of lymphatic metastasis. Recently, aspirin, a non-steroidal anti-inflammatory drug (NSAID), has been reported to inhibit in vivo lymphangiogenesis in tumor and incision wound models, but the mechanisms of actions of aspirin on anti-lymphangiogenesis have been less explored. In this study, we aim to explore the mechanism underlying the anti-lymphangiogenic effects of aspirin in primary human dermal lymphatic microvascular endothelial (HMVEC-dLy) cells in vitro. Pretreatment of aspirin at non-toxic dose 0.3 mM significantly suppressed in vitro cord formation, adhesion, and the migration abilities of the HMVEC-dLy cells. Western blotting analysis indicated that aspirin decreased expression of vascular cell adhesion molecule-1 (VCAM-1), at both protein and mRNA levels, and these correlated with the reduction of NF-κB p65 phosphorylation. By using NF-κB inhibitor (BAY-11-7085) and VCAM-1 siRNA, we showed that VCAM-1 expression is downstream of NF-κB activation, and this NF-κB/VCAM-1 signaling pathway controls cord formation, adhesion, and the migration abilities of the HMVEC-dLy cells. In summary, we demonstrate the potential of aspirin as an anti-lymphangiogenic agent, and elucidate its mechanism of action.
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Mishra, Radhika, Ariunbuyan Sukhbaatar, Shiro Mori, and Tetsuya Kodama. "Abstract P046: CTLA4 targeted therapy using the lymphatic drug delivery system for treatment of metastatic lymph nodes." Cancer Prevention Research 16, no. 1_Supplement (January 1, 2023): P046. http://dx.doi.org/10.1158/1940-6215.precprev22-p046.
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Abstract Background: Metastasis is the prime cause of cancer associated mortality. Lymph nodes (LNs) facilitate the systemic exposure of tumor cells, resulting in fatal systemic metastasis. Treatment of metastatic LNs is therefore imperative. However, successful treatment of metastatic LNs is challenging. Immune checkpoint inhibitor (ICI) therapy is an emerging therapy approved for several advanced malignancies. However, ICI therapy in the context of metastatic LNs remains unexplored due to the absence of reliable models and inquisition techniques. Additionally, while systemically delivered ICI therapy has delivered encouraging results, response is often erratic and mired by unwarranted side effects. To harness the benefits of ICI therapy, it is imperative to uncouple therapeutic response from off-target events. The present study sought to develop an effective intervention strategy using α-CTLA4 mAb for the treatment of metastatic LNs that addresses this unmet need. Methods: Using a murine model of LN metastasis, the therapeutic efficacy of low-dose α-CTLA4 mAb administered to different sites locally, using a novel lymphatic drug delivery system (LDDS) or intraperitoneally (i.p.) was examined. The mouse model was established using luciferase labelled cells in a recombinant inbred strain of mice exhibiting systemic lymphadenopathy (LM8-Luc cells; MXH10/Mo/lpr mice). Results: Therapeutic response was observed in mice treated by all strategies with α-CTLA4 mAb. However, response was erratic in mice administered α-CTLA4 mAb to tumor-free LN through LDDS or intraperitoneally. Strong and fairly consistent therapeutic response was observed upon local delivery of α-CTLA4 mAb through LDDS to tumor-harboring LN. Additionally, incidence of complete response, as indicated by the total-eradication of tumor by the pre-determined experimental endpoint was observed in 66.67% of mice treated by the administration of α-CTLA4 mAb to tumor-harboring LN as opposed to only 33.33% and 28.67% in mice treated by administration of α-CTLA4 mAb to the tumor-free LN or intraperitoneally. Furthermore, treatment using LDDS to tumor-bearing LN was also found to prevent metastases to liver and lung and significantly prolong survival. In stark contrast, treatment through LDDS to tumor-free LN or i.p., worsened survival as opposed to control group, likely due to the onset of immune related adverse events. In keeping with the same, body weight and spleen weights for the i.p. group, which had the worst survival amongst all the experimental groups, was found to drop. Conclusions: Administration strategy is a critical variable that affects ICI therapy associated anti-tumor response and toxicity in the context of metastatic LNs. Therapeutic response is potentiated upon delivery of α-CTLA4 mAb to tumor-harboring LN via LDDS. Citation Format: Radhika Mishra, Ariunbuyan Sukhbaatar, Shiro Mori, Tetsuya Kodama. CTLA4 targeted therapy using the lymphatic drug delivery system for treatment of metastatic lymph nodes. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P046.
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Ovchinnikov, A. Yu, N. A. Miroshnichenko, Yu O. Nikolaeva, and M. M. Vasilyev. "Several studies on the problem of management patients with chronic tonsillitis during periods of remission and exacerbation." Meditsinskiy sovet = Medical Council, no. 16 (November 14, 2020): 109–15. http://dx.doi.org/10.21518/2079-701x-2020-16-109-115.
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Increase in the number of acute and chronic diseases is a global trend. On the one hand, the emergence of new types of viruses, their active mutation, an increase in antibiotic-resistant bacterial strains, a high frequency of immunodeficiency and allergic diseases contribute to this. On the other hand is inadequate treatment of inflammatory diseases of the upper respiratory tract, widespread use of systemic antibiotics without indications. The use of bioregulatory medicines with proven efficacy in the complex treatment can reduce the drug load on the body, reduce the bacterial complications and side effects. Traumeel®S joins the physiological course of inflammation and activates pro-resolving mediators, contributes to its faster completion and tissue repair. The efficacy and safety of Traumeel®S has been confirmed in many randomized clinical trials. The drug has proven its value in almost any inflammatory pathology of the upper respiratory tract and ear. The drug Lymphomyosot®, a multicomponent agent with lymphatic drainage action, has proven itself perfectly in the complex therapy of chronic tonsillitis. In November 2019, the Council of Experts of the National Medical Association of Otorhinolaryngologists on the problems of pathology of the lympharyngeal ring was held. It is recommended to use the multicomponent bioregulatory preparation Traumeel®S to correct the inflammatory process, which has shown in studies a modulating effect on inflammatory mediators without suppressing COX-2 (prostaglandins). With exacerbation of chronic tonsillitis and lymphadenitis of nonspecific etiology, it is possible to use the multicomponent preparation Lymphomyosot®, which helps to improve the drainage and detoxification function of the lymphatic system.
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Hofbauer, Roland, Alan D. Kaye, Stylianos Kapiotis, Oswald Wagner, and Michael Frass. "The Immune System and the Effects of Non-volatile Anesthetics on Neutrophil Transmigration Through Endothelial Cell Monolayers." Current Pharmaceutical Design 5, no. 12 (December 1999): 1015–27. http://dx.doi.org/10.2174/1381612805666230112210939.
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<p>Inflammation represents the consequence of capillary dilation with accumulation of fluid and transmigration of leukocytes into the surrounding tissue. Leukocytes play a major role in the defense system of the body against invading microorganisms. This defense system has a non-specific branch consisting of granulocytes and macrophages and a specific branch of lymphocytes. Granulocytes release cytotoxic compounds from their intracellular granules into their local environment when encountering microorganisms. This random destruction happens rapidly, but it may also harm healthy tissue of the body. Leukocytes patrol the body by circulating through the blood and lymphatic system ensuring a continuous surveillance which is a prerequisite for an efficient defense. Upon tissue damage and inflammation, leukocytes are recruited from the blood to sites of injury, and this trafficking displays exquisite specificity. </p><p> In the late 1890's, Metchnikoff noted the power of certain blood cells to move towards microorganisms and ingest them. In fact, leukocytes adhere to the endothelium of the blood vessels, and subsequently leave the circulation by transmigration through the intercellular junctions of the endothelial cell monolayer. Transmigration is driven by chemoattractants, a process known as diapedesis. Reversible adherence of leukocytes to the endothelium, basement membranes, and other surfaces is an essential event in the establishment of inflammation, whose molecular basis is beginning to be understood. Inflammation may become chronic in many pathophysiologic processes and disease states. </p><p> In long-term mechanically ventilated critically ill patients, non-volatile anesthetics are needed over a prolonged time period. Perioperative infections are a major cause of morbidity and mortality in critically ill patients. Therefore, the influence of non-volatile anesthetics and opioid agents on the immune system is of high interest. </p><p> After presentation of the different effectors of the immune system and their fluxes through the body, the aim of this review is to propose a general model of leukocyte transmigration through endothelial cell monolayers. It emphasizes in which way different non-volatile anesthetic drugs may affect the non-specific branch of the immune system, i.e. the leukocyte transmigration through endothelial cell monolayers.</p>
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Qiao, Jin, Danyang Ji, Shilin Sun, Guangyuan Zhang, Xin Liu, Bingxue Sun, and Qingxiang Guan. "Oral Bioavailability and Lymphatic Transport of Pueraria Flavone-Loaded Self-Emulsifying Drug-Delivery Systems Containing Sodium Taurocholate in Rats." Pharmaceutics 10, no. 3 (September 5, 2018): 147. http://dx.doi.org/10.3390/pharmaceutics10030147.
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We developed self-microemulsifying drug-delivery systems (SMEDDS), including bile salts, to improve the oral bioavailability of pueraria flavones (PFs). The physical properties of the SMEDDS using Cremophor RH 40, and bile salts as mixed surfactants at weight ratios of 10:0–0:10 were determined. The particle sizes of PFs-SMEDDSNR containing sodium taurocholate (NaTC) and Cremophor RH 40, and PFs-SMEDDSR containing Cremophor RH 40 were measured upon dilution with deionized water and other aqueous media. Dilution volume presented no remarkable effects on particle size, whereas dilution media slightly influenced particle size. PFs-SMEDDSNR and PFs-SMEDDSR provided similar release rates in pH-1.2 hydrochloride solution. However, the release rate of PFs-SMEDDSNR was faster than that of PFs-SMEDDSR in pH-6.8 phosphate buffer containing 20 mM NaTC and 500 U/mL porcine pancreas lipase. The pharmacokinetics and bioavailability were measured in rats. The oral bioavailability of PFs-SMEDDSNR was 2.57- and 2.28-fold that of a suspension of PFs (PFs-suspension) before and after the blockade of the lymphatic transport route by cycloheximide, respectively. These results suggested PFs-SMEDDSNR could significantly improve the oral relative absorption of PFs via the lymphatic uptake pathway. SMEDDS containing NaTC may provide an effective approach for enhancing the oral bioavailability of PFs.
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Marshall, Sylvia, Sara Winter, and John D. Capobianco. "Lymphatic osteopathic manipulative treatment reduces duration of deltoid soreness after Pfizer/BioNTech COVID-19 vaccine." Journal of Osteopathic Medicine 122, no. 3 (January 12, 2022): 153–57. http://dx.doi.org/10.1515/jom-2021-0189.
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Abstract Pfizer-BioNTech BNT162b2 is one of the three U.S. Food and Drug Administration (FDA)-approved vaccines for the prevention of COVID-19. Its most common side effect, injection site pain, occurs because of locally recruited inflammatory mediators and is mitigated by the lymphatic system. Side effects may discourage individuals from receiving vaccines; therefore, reducing the duration of injection site pain can promote vaccination compliance. Osteopathic manipulative treatments (OMT) can directly affect the physiology underlying muscle soreness; however, there is currently no literature that supports the use of OMT in this scenario. In this case report, an otherwise healthy male presented with acute left deltoid soreness after receiving the Pfizer COVID-19 vaccine. The pain began 5 h prior to the visit. Three hours after being treated with lymphatic OMT, the severity of the pain was significantly reduced and was alleviated 8h after onset in comparison to the median duration of 24–48 h. He received his second dose 3 weeks later. This case report can provide future studies with the groundwork for further investigating the role of OMT in treating postvaccination muscle soreness, which can improve patient satisfaction and potentially promote vaccination compliance.
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Wang, Hongliang, Lin Li, Jun Ye, Wujun Dong, Xing Zhang, You Xu, Jinping Hu, et al. "Improved Safety and Anti-Glioblastoma Efficacy of CAT3-Encapsulated SMEDDS through Metabolism Modification." Molecules 26, no. 2 (January 18, 2021): 484. http://dx.doi.org/10.3390/molecules26020484.
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13a-(S)-3-pivaloyloxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (CAT3) is a novel oral anti-glioma pro-drug with a potent anti-tumor effect against temozolomide-resistant glioma. 13a(S)-3-hydroxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (PF403) is the active in vivo lipase degradation metabolite of CAT3. Both CAT3 and PF403 can penetrate the blood–brain barrier to cause an anti-glioma effect. However, PF403, which is produced in the gastrointestinal tract and plasma, causes significant gastrointestinal side effects, limiting the clinical application of CAT3. The objective of this paper was to propose a metabolism modification for CAT3 using a self-microemulsifying drug delivery system (SMEDDS), in order to reduce the generation of PF403 in the gastrointestinal tract and plasma, as well as increase the bioavailability of CAT3 in vivo and the amount of anti-tumor substances in the brain. Thus, a CAT3-loaded self-microemulsifying drug delivery system (CAT3-SMEDDS) was prepared, and its physicochemical characterization was systematically carried out. Next, the pharmacokinetic parameters of CAT3 and its metabolite in the rats’ plasma and brain were measured. Furthermore, the in vivo anti-glioma effects and safety of CAT3-SMEDDS were evaluated. Finally, Caco-2 cell uptake, MDCK monolayer cellular transfer, and the intestinal lymphatic transport mechanisms of SMEDDS were investigated in vitro and in vivo. Results show that CAT3-SMEDDS was able to form nanoemulsion droplets in artificial gastrointestinal fluid within 1 min, displaying an ideal particle size (15–30 nm), positive charge (5–9 mV), and controlled release behavior. CAT3-SMEDDS increased the membrane permeability of CAT3 by 3.9-fold and promoted intestinal lymphatic transport. Hence, the bioavailability of CAT3 was increased 79% and the level of its metabolite, PF403, was decreased to 49%. Moreover, the concentrations of CAT3 and PF403 were increased 2–6-fold and 1.3–7.2-fold, respectively, in the brain. Therefore, the anti-glioma effect in the orthotopic models was improved with CAT3-SMEDDS compared with CAT3 in 21 days. Additionally, CAT3-SMEDDS reduced the gastrointestinal side effects of CAT3, such as severe diarrhea, necrosis, and edema, and observed less inflammatory cell infiltration in the gastrointestinal tract, compared with the bare CAT3. Our work reveals that, through the metabolism modification effect, SMEDDS can improve the bioavailability of CAT3 and reduce the generation of PF403 in the gastrointestinal tract and plasma. Therefore, it has the potential to increase the anti-glioma effect and reduce the gastrointestinal side effects of CAT3 simultaneously.
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Devan, Aswathy R., Ayana R. Kumar, Bhagyalakshmi Nair, Nikhil Ponnoor Anto, Amitha Muraleedharan, Bijo Mathew, Hoon Kim, and Lekshmi R. Nath. "Insights into an Immunotherapeutic Approach to Combat Multidrug Resistance in Hepatocellular Carcinoma." Pharmaceuticals 14, no. 7 (July 9, 2021): 656. http://dx.doi.org/10.3390/ph14070656.
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Hepatocellular carcinoma (HCC) has emerged as one of the most lethal cancers worldwide because of its high refractoriness and multi-drug resistance to existing chemotherapies, which leads to poor patient survival. Novel pharmacological strategies to tackle HCC are based on oral multi-kinase inhibitors like sorafenib; however, the clinical use of the drug is restricted due to the limited survival rate and significant side effects, suggesting the existence of a primary or/and acquired drug-resistance mechanism. Because of this hurdle, HCC patients are forced through incomplete therapy. Although multiple approaches have been employed in parallel to overcome multidrug resistance (MDR), the results are varying with insignificant outcomes. In the past decade, cancer immunotherapy has emerged as a breakthrough approach and has played a critical role in HCC treatment. The liver is the main immune organ of the lymphatic system. Researchers utilize immunotherapy because immune evasion is considered a major reason for rapid HCC progression. Moreover, the immune response can be augmented and sustained, thus preventing cancer relapse over the post-treatment period. In this review, we provide detailed insights into the immunotherapeutic approaches to combat MDR by focusing on HCC, together with challenges in clinical translation.
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Elshama, Said Said, Metwally E. Abdallah, and Rehab I. Abdel-Karim. "Zinc Oxide Nanoparticles: Therapeutic Benefits and Toxicological Hazards." Open Nanomedicine Journal 5, no. 1 (July 19, 2018): 16–22. http://dx.doi.org/10.2174/1875933501805010016.
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Despite the widespread application of zinc oxide nanoparticles in biomedicine, their use is still a controversial issue. Zinc oxide nanoparticles were reported to have therapeutic benefits. However, they were reported to have toxicological hazards as well. Several studies reported the antibacterial, anticancer, antioxidant, and immunomodulatory effects of zinc oxide nanoparticles. Additionally, zinc oxide nanoparticles were used in sunscreens. Furthermore, the ability to use zinc oxide nanoparticles as an adjuvant treatment to alleviate the toxic effects of chemotherapeutic drugs has been reported. However, zinc oxide nanoparticles were shown to induce toxic effects in different body organs and systems. The affected organs included liver, spleen, kidney, stomach, pancreas, heart and lung. In addition, zinc oxide nanoparticles were reported to adversely affect the neurological system, lymphatic system, hematological indices, sex hormones levels, and fetal development. The toxic effects of zinc oxide nanoparticles were based on their concentration, their dose, the route of their administration, and the time of exposure to those particles. Thus, it is crucial to assess their efficacy and safety to determine their toxicological risks and therapeutic benefits.
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Kutova, Olga, Evgenii Guryev, Evgeniya Sokolova, Razan Alzeibak, and Irina Balalaeva. "Targeted Delivery to Tumors: Multidirectional Strategies to Improve Treatment Efficiency." Cancers 11, no. 1 (January 10, 2019): 68. http://dx.doi.org/10.3390/cancers11010068.
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Malignant tumors are characterized by structural and molecular peculiarities providing a possibility to directionally deliver antitumor drugs with minimal impact on healthy tissues and reduced side effects. Newly formed blood vessels in malignant lesions exhibit chaotic growth, disordered structure, irregular shape and diameter, protrusions, and blind ends, resulting in immature vasculature; the newly formed lymphatic vessels also have aberrant structure. Structural features of the tumor vasculature determine relatively easy penetration of large molecules as well as nanometer-sized particles through a blood–tissue barrier and their accumulation in a tumor tissue. Also, malignant cells have altered molecular profile due to significant changes in tumor cell metabolism at every level from the genome to metabolome. Recently, the tumor interaction with cells of immune system becomes the focus of particular attention, that among others findings resulted in extensive study of cells with preferential tropism to tumor. In this review we summarize the information on the diversity of currently existing approaches to targeted drug delivery to tumor, including (i) passive targeting based on the specific features of tumor vasculature, (ii) active targeting which implies a specific binding of the antitumor agent with its molecular target, and (iii) cell-mediated tumor targeting.
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Souza, Dziedzom De, Collins Stephen Ahorlu, Joseph Otchere, Sedzro Mensah, Sudan Adu-Amankwah, and Daniel Boakye. "PO 8239 BASELINE ASSESSMENT OF LYMPHATIC FILARIASIS IN 18 COMMUNITIES IN WESTERN GHANA BEFORE THE IMPLEMENTATION OF TWICE-YEARLY TREATMENT." BMJ Global Health 4, Suppl 3 (April 2019): A22.3—A23. http://dx.doi.org/10.1136/bmjgh-2019-edc.57.
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BackgroundLymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as a public health problem by 2020, with the main strategy being treatment of entire endemic communities. Since the inception of the Global Programme for the Elimination of LF in 2000, tremendous progress has been made in many endemic countries. However, current observations point to the need for improved treatment regimen, frequency of treatment or drug delivery strategies in order to achieve the elimination goals in certain endemic areas. In this randomised trial, we evaluate the use of twice-yearly treatment with ivermectin and albendazole in 18 LF-endemic communities in Ghana, where despite 15 years of yearly treatment the disease is still above the elimination thresholds.MethodsFollowing demographic data collection, Wuchereria bancrofti antigen, microfilaria and antibody prevalence were assessed in study participants using the Alere FTS kit, nucleopore filtration and Wb123 ELISA, respectively. The study assessed the perspectives of the communities’on persistent transmission of LF in view of implementing effective treatment uptake strategies.ResultsThe baseline assessments revealed antigen prevalence of 8.2% (95% CI=6.8–9.8), with overall microfilaria prevalence of 1.2%. Infections were higher in males and in individuals who spend significant amount of time outdoors for commercial activities. Barriers related to medication, personal, health system, disease and social structure were observed to affect mass drug administration compliance. Community members perceived that they were not susceptible to infection and this together with drug adverse effects strongly affect the ingestion of the drugs.ConclusionWhile this trial is still in an early phase, the baseline assessments reveal programmatic challenges to the implementation of a twice-yearly treatment strategy for the control of LF which must be addressed to enhance implementation success.
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Fatih Kocyigit, Burhan. "CAN MANUAL THERAPY AND MASSAGE BE USED AS COMPLEMENTARY METHODS FOR FEMALE INFERTILITY IN DIFFERENT AGE GROUPS?" Anti-Aging Eastern Europe 1, no. 2 (December 28, 2022): 118–22. http://dx.doi.org/10.56543/aaeeu.2022.1.2.06.
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Infertility is the inability to conceive after one year of unprotected intercourse, and about one in six couples deal with this issue. Nearly half of the factors contributing to a couple’s infertility are female-related, and the underlying cause is variable. Many treatment options can be used depending on the underlying cause of infertility. The available treatments often include in vitro fertilization, intrauterine insemination, and fertility-inducing drugs. Numerous couples favor complementary medicine alongside conventional treatments to enhance treatment efficacy and reduce side effects. Manual therapy and massage are among these complementary treatment approaches. Manual therapy is defined in various ways. One of them is manipulating and mobilizing soft tissue structures and related joints using the hands. Manual therapy can alleviate pain, reduce inflammation, prevent contracture formation, manage existing contractures, increase range of motion, aid mobilization, and improve overall health. It contains a variety of massage treatments, stretching, and mobilization applications. Manual therapy and massage can be administered to manage various disorders, from pediatric to geriatric populations. These are safe interventions. Manual therapy and massage have beneficial effects on the management of female infertility. These methods reduce adhesions and mobilize organs in the pelvic region. They have positive effects on circulatory system disorders, including lymphatic drainage abnormalities. Overcoming reproductive system lymphatic drainage and circulation difficulties can result in balanced hormone levels, regular menstrual cycles, and pregnancies. In addition, manual therapy and massage improve the psychological state of individuals in a way that will benefit the management of female infertility.
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Byrne, Andrew J., Sandra A. Bright, James P. McKeown, John E. O’Brien, Brendan Twamley, Darren Fayne, D. Clive Williams, and Mary J. Meegan. "Design, Synthesis and Biochemical Evaluation of Novel Ethanoanthracenes and Related Compounds to Target Burkitt’s Lymphoma." Pharmaceuticals 13, no. 1 (January 17, 2020): 16. http://dx.doi.org/10.3390/ph13010016.
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Lymphomas (cancers of the lymphatic system) account for 12% of malignant diseases worldwide. Burkitt’s lymphoma (BL) is a rare form of non-Hodgkin’s lymphoma in which the cancer starts in the immune B-cells. We report the synthesis and preliminary studies on the antiproliferative activity of a library of 9,10-dihydro-9,10-ethanoanthracene based compounds structurally related to the antidepressant drug maprotiline against BL cell lines MUTU-1 and DG-75. Structural modifications were achieved by Diels-Alder reaction of the core 9-(2-nitrovinyl)anthracene with number of dienophiles including maleic anhydride, maleimides, acrylonitrile and benzyne. The antiproliferative activity of these compounds was evaluated in BL cell lines EBV− MUTU-1 and EBV+ DG-75 (chemoresistant). The most potent compounds 13j, 15, 16a, 16b, 16c, 16d and 19a displayed IC50 values in the range 0.17–0.38 μM against the BL cell line EBV− MUTU-1 and IC50 values in the range 0.45–0.78 μM against the chemoresistant BL cell line EBV+ DG-75. Compounds 15, 16b and 16c demonstrated potent ROS dependent apoptotic effects on the BL cell lines which were superior to the control drug taxol and showed minimal cytotoxicity to peripheral blood mononuclear cells (PBMCs). The results suggest that this class of compounds merits further investigation as antiproliferative agents for BL.
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Cho, In Kyung, Man Kyu Shim, Wooram Um, Jong-Ho Kim, and Kwangmeyung Kim. "Light-Activated Monomethyl Auristatin E Prodrug Nanoparticles for Combinational Photo-Chemotherapy of Pancreatic Cancer." Molecules 27, no. 8 (April 14, 2022): 2529. http://dx.doi.org/10.3390/molecules27082529.
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Pancreatic cancer is a highly fatal disease that is becoming an increasingly leading cause of cancer-related deaths. In clinic, the most effective approach to treat pancreatic cancers is the combination treatment of several chemotherapeutic drugs, including fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), but this approach is not adequate to manage patients due to their severe toxic side effects. Herein, we proposed light-activated monomethyl auristatin E (MMAE) prodrug nanoparticles for combinational photo-chemotherapy and optimized its applications for pancreatic cancer treatment. The photosensitizer (Ce6) and chemotherapeutic drug (MMAE) were conjugated through caspase-3-specific cleavable peptide (KGDEVD). The resulting CDM efficiently promoted the reactive oxygen species (ROS) under visible light irradiation and thereby induced caspase-3 overexpression in pacreatic cancers, which subsequently released the MMAE from the system. Importantly, MMAE released from CDM further amplified the activation of CDM into MMAE by inducing extensive apoptotic cell death in tumor microenvironment for treatment of tumor cells in deep in the tumor tissues as far visible light cannot reach. In addition, CDM formed prodrug nanoparticles via intermolecular π-π stacking and hydrophobic interactions, allowing durable and reliable treatment by preventing fast leakage from the pancreatic cancers via the lymphatic vessels. The CDM directly (intratumoral) injected into pancreatic cancers in orthotopic models through an invasive approach significantly delayed the tumor progression by combinational photo-chemotherapy with less toxic side effects. This study offers a promising and alternative approach for safe and more effective pancreatic cancer treatment via prodrug nanoparticles that combine photodynamic therapy and chemotherapy.
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Rankin, Alexander W., Aparna Annam, Kathryn Chatfield, Lauren R. Hill, Ann Kulungowski, Leslie McCallen, and Taizo A. Nakano. "Trametinib for Refractory Chylous Effusions in Children with Noonan Syndrome." Blood 138, Supplement 1 (November 5, 2021): 3140. http://dx.doi.org/10.1182/blood-2021-145902.
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Abstract BACKGROUND Noonan syndrome (NS) is one of several autosomal dominant multisystem disorders known as RASopathies. Common manifestations of NS include congenital heart defects and cardiomyopathy, lymphatic malformations, and predisposition to myeloproliferative disorders. Chylous fluid accumulation secondary to lymphatic malformations are seen in NS and are a major cause of morbidity and mortality often refractory to conventional medical management. There has been increasing interest in the use of pharmacologic MEK inhibition in the management of these patients given that activating RAS pathway mutations lead to downstream MEK activation that is causative of this pathology. DESIGN/METHODS Three patients with a confirmed diagnosis of NS are described. Each patient developed complications from chylous effusions refractory to conventional management and were subsequently enrolled on-study to treat with compassionate use oral trametinib from Novartis Pharmaceuticals on a single patient Investigational New Drug from the Food and Drug Administration (FDA). All patients were consented to be monitored for one year of therapy following a local protocol approved by the Colorado Institutional Review Board (COMIRB). Patient 1: a 4-year-old female with NS due to a pathogenic germline mutation of the RIT1 gene [c.246T>G, p.Phe82Leu] born with severe hypertrophic cardiomyopathy, mitral valve dysplasia, and pulmonary valve stenosis. She developed bilateral chylous pleural effusions that were refractory to dietary modification, diuretics, octreotide, and sirolimus. Patient 2: a 3-month-old female with NS due to a pathogenic germline mutation of the SOS1 gene [c.1322G>A; p.Cys441Tyr] born with esophageal atresia/tracheoesophageal fistula and moderate pulmonary valve stenosis. She developed bilateral chylous pleural effusions and ascites that were refractory to dietary modification and octreotide therapy. Patient 3: a 4-month-old male with NS due to a gain-of-function mutation of PTPN11 [c.854T>C; p.Phe285Ser] with hypertrophic cardiomyopathy, pulmonary valve stenosis, respiratory insufficiency with suspected pulmonary lymphangiectasia, and persistent chylous pleural effusions in addition to Noonan syndrome-associated myeloproliferative disorder (NS-MPD) that had been refractory to traditional management. RESULTS MEK inhibition with trametinib was used in three patients with NS and life-threatening complications with no medical or surgical treatment options. All three patients had dynamic contrast magnetic resonance lymphangiography (DCMRL) evidence of primary, central lymphatic dysplasia that manifested in lymphatic accumulation affecting cardiorespiratory function, nutrition, and the immune system. DCMRL imaging for patient 2 are highlighted in Figure 1 A and B. Within one month of initiating trametinib oral therapy, all three patients demonstrated response adequate to wean from mechanical ventilation and other supportive care modalities. Serum albumin levels improved as lymphatic leak resolved (Figure 1C). Patient 3 showed improvement in hypertrophic cardiomyopathy as evidenced by a decrease in both NT-proBNP and left ventricular mass by echocardiogram. Patients 1 and 2 demonstrated notable improvements in growth after one year of therapy, with increase in both weight and height percentiles. Patient 3 also presented with NS-MPD that responded with marked improvements in total WBC count as well as absolute monocyte count (Figure 1D). DISCUSSION Our experience adds to the growing body of evidence demonstrating the effectiveness of MEK inhibition on disease processes that are common in patients with NS and other RASopathies. None of the patients in our series experienced significant adverse effects from the medication aside from patient 2 who developed mild dermatitis. The efficacy of this therapy does not appear to be based on the underlying genotype, as each of the three patients we describe had different underlying molecular alterations (SOS1, RIT1, PTPN11). Substantial improvements in a variety of parameters including lymphatic malformations, cardiomyopathy, pulmonary valve stenosis, growth, and NS-MPD highlight the potential utility of trametinib in this patient population. Larger, prospective studies are necessary to confirm the efficacy of MEK inhibition and to assess the long-term safety of its use in this population. Figure 1 Figure 1. Disclosures Nakano: Novartis: Consultancy. OffLabel Disclosure: Trametinib is a MEK1/2 inhibitor that has been approved for the use in certain malignancies. Its off label use in children with Noonan Syndrome with significant lymphatic anomalies is based on the up regulation of the MAPK pathway in these patients.
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Chai, Jong-Yil, Bong-Kwang Jung, and Sung-Jong Hong. "Albendazole and Mebendazole as Anti-Parasitic and Anti-Cancer Agents: an Update." Korean Journal of Parasitology 59, no. 3 (June 21, 2021): 189–225. http://dx.doi.org/10.3347/kjp.2021.59.3.189.
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The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment of parasitic infections, as well as cancers, is briefly reviewed. These drugs are known to block the microtubule systems of parasites and mammalian cells leading to inhibition of glucose uptake and transport and finally cell death. Eventually they exhibit ovicidal, larvicidal, and vermicidal effects on parasites, and tumoricidal effects on hosts. Albendazole and mebendazole are most frequently prescribed for treatment of intestinal nematode infections (ascariasis, hookworm infections, trichuriasis, strongyloidiasis, and enterobiasis) and can also be used for intestinal tapeworm infections (taeniases and hymenolepiasis). However, these drugs also exhibit considerable therapeutic effects against tissue nematode/cestode infections (visceral, ocular, neural, and cutaneous larva migrans, anisakiasis, trichinosis, hepatic and intestinal capillariasis, angiostrongyliasis, gnathostomiasis, gongylonemiasis, thelaziasis, dracunculiasis, cerebral and subcutaneous cysticercosis, and echinococcosis). Albendazole is also used for treatment of filarial infections (lymphatic filariasis, onchocerciasis, loiasis, mansonellosis, and dirofilariasis) alone or in combination with other drugs, such as ivermectin or diethylcarbamazine. Albendazole was tried even for treatment of trematode (fascioliasis, clonorchiasis, opisthorchiasis, and intestinal fluke infections) and protozoan infections (giardiasis, vaginal trichomoniasis, cryptosporidiosis, and microsporidiosis). These drugs are generally safe with few side effects; however, when they are used for prolonged time (>14-28 days) or even only 1 time, liver toxicity and other side reactions may occur. In hookworms, Trichuris trichiura, possibly Ascaris lumbricoides, Wuchereria bancrofti, and Giardia sp., there are emerging issues of drug resistance. It is of particular note that albendazole and mebendazole have been repositioned as promising anti-cancer drugs. These drugs have been shown to be active in vitro and in vivo (animals) against liver, lung, ovary, prostate, colorectal, breast, head and neck cancers, and melanoma. Two clinical reports for albendazole and 2 case reports for mebendazole have revealed promising effects of these drugs in human patients having variable types of cancers. However, because of the toxicity of albendazole, for example, neutropenia due to myelosuppression, if high doses are used for a prolonged time, mebendazole is currently more popularly used than albendazole in anti-cancer clinical trials.
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Choudhari, Jyoti Kant. "An perspective: Potential medicinal plant resources for filariasis disease." CSVTU International Journal of Biotechnology Bioinformatics and Biomedical 3, no. 3 (February 18, 2019): 41–49. http://dx.doi.org/10.30732/ijbbb.20180303002.
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Filariasis is one of the oldest and most debilitating neglected tropical diseases, which is caused by parasitic filarial worm that are transmitted to humans by mosquitoes. In the lymphatics system filarial worm become adult worm that cause damage to lymphatics resulting in dilatation of lymph vessels. An estimated approximately 120 million people in 83 countries. An estimated approximately one and half billion live in areas where filariasis is endemic and are at risk of infection with Wuchereria bancrofti, Brugia timori and Brugia malayi. Presently diethylcarbamazine and Ivermectin and a single-dose treatment are currently employing in an attempt to control the infection but these drugs cannot treat properly and have lots of side effects. Recently limited plant products were reported to be beneficial in the treatment or control of these parasitic infections like filariasis but they could not be developed into viable drugs for a variety of reasons. This review focuses on searching medicinal plants for filariasis diseases. In this review, we explored medicinal plant that show the anti-filarial activities on filarial worm. These medical plants will help for further development the potation drug development for the treatment
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Kobold, Sebastian, Angela Krackhardt, Hans Schlösser, and Dominik Wolf. "Immunonkologie – ein Überblick." DMW - Deutsche Medizinische Wochenschrift 143, no. 14 (July 2018): 1006–13. http://dx.doi.org/10.1055/a-0623-9147.
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AbstractPioneering work has unraveled the role of the immune system in the development and control of cancer. This knowledge has set the basis for the successful implementation of immunotherapy into the standard of care for a large number of cancer types. Based on response rates and prolongation of overall survival, immunotherapeutic approaches have been approved in a growing number of tumor diseases. Activation or therapeutic utilization of T cells represent the basis of these concepts. Checkpoint inhibitory antibodies inhibiting CTLA-4, PD1 and PD-L1 receptors and ligands induce long-term clinical tumor control in a significant number of cancer patients including metastatic melanoma and non-small cell lung cancer. As an alternative concept of T cell activation, the dual CD19 – CD3 targeting bispecific antibody blinatumomab has been approved for refractory acute lymphatic B-cell leukemia (ALL). Moreover, T cells genetically engineered with an anti-CD19-chimeric antigen receptor have also been approved for ALL and malignant B-cell lymphoma by the food and drug administration (FDA). In all of these immunotherapies, severe side effects may occur and require a well-trained team of physicians. Moreover, the growing number of clinically investigated and validated novel compounds as well as cellular therapeutics accentuate the complexity and challenge of this treatment modality. This review highlights the most prominent recent clinical developments in the field of immuno-oncology.
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Masiello, Timothy, Atul Dhall, L. Hemachandra, Natalya Tokranova, J. Melendez, and James Castracane. "A Dynamic Culture Method to Produce Ovarian Cancer Spheroids under Physiologically-Relevant Shear Stress." Cells 7, no. 12 (December 19, 2018): 277. http://dx.doi.org/10.3390/cells7120277.
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The transcoelomic metastasis pathway is an alternative to traditional lymphatic/hematogenic metastasis. It is most frequently observed in ovarian cancer, though it has been documented in colon and gastric cancers as well. In transcoelomic metastasis, primary tumor cells are released into the abdominal cavity and form cell aggregates known as spheroids. These spheroids travel through the peritoneal fluid and implant at secondary sites, leading to the formation of new tumor lesions in the peritoneal lining and the organs in the cavity. Models of this process that incorporate the fluid shear stress (FSS) experienced by these spheroids are few, and most have not been fully characterized. Proposed herein is the adaption of a known dynamic cell culture system, the orbital shaker, to create an environment with physiologically-relevant FSS for spheroid formation. Experimental conditions (rotation speed, well size and cell density) were optimized to achieve physiologically-relevant FSS while facilitating the formation of spheroids that are also of a physiologically-relevant size. The FSS improves the roundness and size consistency of spheroids versus equivalent static methods and are even comparable to established high-throughput arrays, while maintaining nearly equivalent viability. This effect was seen in both highly metastatic and modestly metastatic cell lines. The spheroids generated using this technique were fully amenable to functional assays and will allow for better characterization of FSS’s effects on metastatic behavior and serve as a drug screening platform. This model can also be built upon in the future by adding more aspects of the peritoneal microenvironment, further enhancing its in vivo relevance.
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Chaudhary, Roobal, and Ravinesh Mishra. "Nano-formulations: Recent Trends for Ocular Bioavailability Enhancement." Journal of Drug Delivery and Therapeutics 12, no. 2-S (April 20, 2022): 225–33. http://dx.doi.org/10.22270/jddt.v12i2-s.5301.
Full textAbstract:
Eye is a critical part of the body that is readily available and with damage having direct effects on the life of an individual. Delivery of ocular drugs always remain challenging for healthcare professionals and scientists all over the world due to the challenges that dynamic opthalamic environment provides. These challenges involves different barriers like corneal epithelium, corneal stroma, sclera and other bio-membranes (static barriers), choroidal or conjunctival blood flow, lymphatic clearance, tear turnover (dynamic barriers) and efflux pumps/enzymes(metabolic barriers).Ocular diseases include various diseases affecting different parts of the eye. The eye presents comprehensive perspectives and difficulties in the distribution of medicaments, primarily due to the exceptional ability inherent in this mechanism for drugs to enter the main circulatory system and also for eye barrier limitations. Even if conventional non-invasive and invasive treatments like eye drops, injectable preparations and implantable devices are available but these treatments either have bioavailability issues or serious adverse eye effects. Additionally, the new concept of nanoscience and nano-technology gives new a pathway for treating ocular disease. Different active molecules were engineered to communicate with nano-carriers to pass these eye barriers and interact closely with unique specific eye tissues. This study highlights the latest advances in nano-formulations for ophthalmic diagnosis and provides discussions in the mainstream of opthalamic diseases about the role of nano-formulations in nearby future.
Keywords: ocular diseases, nano-technology, static barrier, dynamic barrier, nano-carriers, bioavailability.
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Chaudhary, Roobal, and Ravinesh Mishra. "Nano-formulations: Recent Trends for Ocular Bioavailability Enhancement." Journal of Drug Delivery and Therapeutics 12, no. 2-S (April 20, 2022): 225–33. http://dx.doi.org/10.22270/jddt.v12i2-s.5301.
Full textAbstract:
Eye is a critical part of the body that is readily available and with damage having direct effects on the life of an individual. Delivery of ocular drugs always remain challenging for healthcare professionals and scientists all over the world due to the challenges that dynamic opthalamic environment provides. These challenges involves different barriers like corneal epithelium, corneal stroma, sclera and other bio-membranes (static barriers), choroidal or conjunctival blood flow, lymphatic clearance, tear turnover (dynamic barriers) and efflux pumps/enzymes(metabolic barriers).Ocular diseases include various diseases affecting different parts of the eye. The eye presents comprehensive perspectives and difficulties in the distribution of medicaments, primarily due to the exceptional ability inherent in this mechanism for drugs to enter the main circulatory system and also for eye barrier limitations. Even if conventional non-invasive and invasive treatments like eye drops, injectable preparations and implantable devices are available but these treatments either have bioavailability issues or serious adverse eye effects. Additionally, the new concept of nanoscience and nano-technology gives new a pathway for treating ocular disease. Different active molecules were engineered to communicate with nano-carriers to pass these eye barriers and interact closely with unique specific eye tissues. This study highlights the latest advances in nano-formulations for ophthalmic diagnosis and provides discussions in the mainstream of opthalamic diseases about the role of nano-formulations in nearby future.
Keywords: ocular diseases, nano-technology, static barrier, dynamic barrier, nano-carriers, bioavailability.
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Hasan, Djo, Atsuko Shono, Coenraad K. van Kalken, Peter J. van der Spek, Eric P. Krenning, and Toru Kotani. "A novel definition and treatment of hyperinflammation in COVID-19 based on purinergic signalling." Purinergic Signalling 18, no. 1 (November 10, 2021): 13–59. http://dx.doi.org/10.1007/s11302-021-09814-6.
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AbstractHyperinflammation plays an important role in severe and critical COVID-19. Using inconsistent criteria, many researchers define hyperinflammation as a form of very severe inflammation with cytokine storm. Therefore, COVID-19 patients are treated with anti-inflammatory drugs. These drugs appear to be less efficacious than expected and are sometimes accompanied by serious adverse effects. SARS-CoV-2 promotes cellular ATP release. Increased levels of extracellular ATP activate the purinergic receptors of the immune cells initiating the physiologic pro-inflammatory immune response. Persisting viral infection drives the ATP release even further leading to the activation of the P2X7 purinergic receptors (P2X7Rs) and a severe yet physiologic inflammation. Disease progression promotes prolonged vigorous activation of the P2X7R causing cell death and uncontrolled ATP release leading to cytokine storm and desensitisation of all other purinergic receptors of the immune cells. This results in immune paralysis with co-infections or secondary infections. We refer to this pathologic condition as hyperinflammation. The readily available and affordable P2X7R antagonist lidocaine can abrogate hyperinflammation and restore the normal immune function. The issue is that the half-maximal effective concentration for P2X7R inhibition of lidocaine is much higher than the maximal tolerable plasma concentration where adverse effects start to develop. To overcome this, we selectively inhibit the P2X7Rs of the immune cells of the lymphatic system inducing clonal expansion of Tregs in local lymph nodes. Subsequently, these Tregs migrate throughout the body exerting anti-inflammatory activities suppressing systemic and (distant) local hyperinflammation. We illustrate this with six critically ill COVID-19 patients treated with lidocaine.
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Gudina Mekonnen, Ayana, and Fayisa Wakgari Oljira. "Review on epidemiology of bovine hemoparasites in Ethiopia." Insights in Veterinary Science 6, no. 1 (April 29, 2022): 013–16. http://dx.doi.org/10.29328/journal.ivs.1001036.
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A literature-based review was made to assess available information on bovine hemoparasites related to their epidemiology, distribution, and economic importance in Ethiopia. Babesiosis, anaplasmosis, cowdriosis, theileriosis, and trypanosomosis are the major hemo-parasitic disease of bovine in Ethiopia. Their adverse effects on the health of the animals can decrease production and productivity. Hemoparasites generally cause fever, anemia, jaundice, anorexia, weight loss, milk drop, malaise, swelling of lymph nodes, dyspnoea, diarrhea, nervous disorders, and death by affecting blood vessels and/or lymphatic system of the animal. Reports from different parts of the country displayed there is a high distribution of bovine hemoparastic disease throughout the country. Anaplasmosis, Babesiosis (redwater), Ehlichiosis (Heartwater), Theileriosis, and Trypanosomosis are the major hemoparasitic diseases with heavy economic losses. Their mode of transmission was by arthropod vectors ticks and flies. Applying effective vector control and using vaccines drugs are the two most important control methods for hemoparasites diseases. Also having knowledge of parasite life cycles, their biological vector, and the immune response of bovines to vectors and parasites were also used in the successful application of control strategies. Creating awareness of the mode of transmission, method of control, and prevention of hemoparastic disease of bovine to livestock owners were warranted to decrease the effect of the disease.
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Hsu, Ching-Yun, Pei-Wen Wang, Ahmed Alalaiwe, Zih-Chan Lin, and Jia-You Fang. "Use of Lipid Nanocarriers to Improve Oral Delivery of Vitamins." Nutrients 11, no. 1 (January 1, 2019): 68. http://dx.doi.org/10.3390/nu11010068.
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The chemical environment and enzymes in the gastrointestinal (GI) membrane limit the oral absorption of some vitamins. The GI epithelium also contributes to the poor permeability of numerous antioxidant agents. Thus, lipophilic vitamins do not readily dissolve in the GI tract, and therefore they have low bioavailability. Nanomedicine has the potential to improve the delivery efficiency of oral vitamins. In particular, the use of lipid nanocarriers for certain vitamins that are administered orally can provide improved solubility, chemical stability, epithelium permeability and bioavailability, half-life, nidus targeting, and fewer adverse effects. These lipid nanocarriers include self-emulsifying drug delivery systems (SEDDSs), nanoemulsions, microemulsions, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs). The use of nontoxic excipients and sophisticated material engineering of lipid nanosystems allows for control of the physicochemical properties of the nanoparticles and improved GI permeation via mucosal or lymphatic transport. In this review, we highlight recent progress in the development of lipid nanocarriers for vitamin delivery. In addition, the same lipid nanocarriers used for vitamins may also be effective as carriers of vitamin derivatives, and therefore enhance their oral bioavailability. One example is the incorporation of d-α-tocopheryl polyethylene glycol succinate (TPGS) as the emulsifier in lipid nanocarriers to increase the solubility and inhibit P-glycoprotein (P-gp) efflux. We also survey the concepts and discuss the mechanisms of nanomedical techniques that are used to develop vitamin-loaded nanocarriers.
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Czarnecki, A. "Gemcitabine and radiotherapy: Analysis of safe use." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 18146. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.18146.
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18146 Background: Radiation in combination with chemotherapy offers a significant survival advantage. Preclinical and clinical data indicate that gemcitabine (GEM) is a potent radiosensitizing agent in numerous cancer types used subsequently with radiation given in different doses and techniques. We compared safety/toxic effects of GEM with GEM plus radiation. Methods: Lilly Safety Database was searched for all reports where patients received radiation before, during and after GEM therapy. The string search for ‘radio’, ‘radia’ and a search for MedDRA terms covering possible radiation recall and typical recall phenomena were conducted. Cases were reviewed by a physician and allocated to one of the categories: ‘concurrent’ (radiation and GEM was given at the same time or 7 days apart), and ‘non-concurrent’ (treatment was given more than 7 days apart). Results: In one third of cases who received concurrent treatment the toxicity reported was higher in 3 System Organ Classes (SOC): ‘Injury’, ‘Gastrointestinal disorders’ (GI), and ‘Respiratory’ in comparison to non radiation treated patients: 4.1%, 16%, 14.8% versus 1.4%, 11.2% and 10.5% respectively but toxicity was lower for ‘Blood and lymphatic disorders’ and ‘General disorders’. In cases with ‘non-concurrent’ treatment the results were similar to ‘concurrent’ treatment for the Injury, Respiratory and Blood SOCs but GI toxicity was only 60% of the one seen in non radiation treated patients. In patients with reported radiation recall the most frequent were skin reactions, pneumonitis and myositis. Radiation injury mainly affected targeted tissue organs exposed to direct radiation e.g eosophagitis and pneumonitis for chest irradiation, GI effects for abdominal irradiation. In Non-concurrent administration no correlation between GEM dose and toxicity could be established. In Concurrent cases, treatment dose and technique of radiation, target tissue and volume were factors together with dose and frequency of GEM administration. Conclusions: Review of adverse drug reactions for GEM and radiation treatment reported from estimated GEM exposure of nearly 1.1 million patients suggests that any increase in GEM toxicity in non- concurrent combination regimen other than radiation recall is due to typical radiation toxicity and mainly affects directly irradiated tissues. No significant financial relationships to disclose.
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Sunkari, Keerthi Reddy, and Pallavi Sunduru. "Lymphatic System: A Path for Drug Delivery." International Journal of Advances in Pharmacy and Biotechnology 6, no. 2 (July 31, 2020): 14–18. http://dx.doi.org/10.38111/ijapb.20200602003.
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HATAKEYAMA, Yuriko, Sax NICOLAS, Shigeki KATO, Maya SAKAMOTO, Shiro MORI, and Tetsuya KODAMA. "J026012 Development of Lymphatic drug delivery system." Proceedings of Mechanical Engineering Congress, Japan 2012 (2012): _J026012–1—_J026012–5. http://dx.doi.org/10.1299/jsmemecj.2012._j026012-1.
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Marti, Daniela, Dorina Coricovac, Iulia Pinzaru, Anca Isaia, Razvan Susan, Daniela Ionescu, Oana Suciu, Monica Susan, and Voichita Lazureanu. "Drug Delivery Systems for Lymphatic Uptake." Revista de Chimie 68, no. 12 (January 15, 2018): 2902–6. http://dx.doi.org/10.37358/rc.17.12.6003.
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The lymphatic system is considered to be the second circulatory system within the body, responsible for the maintenance of fluid homeostasis and immune protection. Among the aforementioned roles, it was proved that lymphatics are involved in dissemination of cancer and infections. This review offers a short description of the physiological features of lymphatic network, the lymphatic transport and the main drug delivery systems for lymphatic uptake.
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HATAKEYAMA, Yuriko, Shigeki KATO, Maya SAKAMOTO, Shiro MORI, and Tetsuya KODAMA. "J023015 Dynamic image of the lymphatic vessel using lymphatic drug delivery system." Proceedings of Mechanical Engineering Congress, Japan 2013 (2013): _J023015–1—_J023015–4. http://dx.doi.org/10.1299/jsmemecj.2013._j023015-1.
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Xu, Wenjing, Natalie R. Harris, and Kathleen M. Caron. "Lymphatic Vasculature: An Emerging Therapeutic Target and Drug Delivery Route." Annual Review of Medicine 72, no. 1 (January 27, 2021): 167–82. http://dx.doi.org/10.1146/annurev-med-051419-114417.
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The lymphatic system has received increasing scientific and clinical attention because a wide variety of diseases are linked to lymphatic pathologies and because the lymphatic system serves as an ideal conduit for drug delivery. Lymphatic vessels exert heterogeneous roles in different organs and vascular beds, and consequently, their dysfunction leads to distinct organ-specific outcomes. Although studies in animal model systems have led to the identification of crucial lymphatic genes with potential therapeutic benefit, effective lymphatic-targeted therapeutics are currently lacking for human lymphatic pathological conditions. Here, we focus on the therapeutic roles of lymphatic vessels in diseases and summarize the promising therapeutic targets for modulating lymphangiogenesis or lymphatic function in preclinical or clinical settings. We also discuss considerations for drug delivery or targeting of lymphatic vessels for treatment of lymphatic-related diseases. The lymphatic vasculature is rapidly emerging as a critical system for targeted modulation of its function and as a vehicle for innovative drug delivery.
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Fourie, Kezia R., and Heather L. Wilson. "Understanding GroEL and DnaK Stress Response Proteins as Antigens for Bacterial Diseases." Vaccines 8, no. 4 (December 17, 2020): 773. http://dx.doi.org/10.3390/vaccines8040773.
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Bacteria do not simply express a constitutive panel of proteins but they instead undergo dynamic changes in their protein repertoire in response to changes in nutritional status and when exposed to different environments. These differentially expressed proteins may be suitable to use for vaccine antigens if they are virulence factors. Immediately upon entry into the host organism, bacteria are exposed to a different environment, which includes changes in temperature, osmotic pressure, pH, etc. Even when an organism has already penetrated the blood or lymphatics and it then enters another organ or a cell, it can respond to these new conditions by increasing the expression of virulence factors to aid in bacterial adherence, invasion, or immune evasion. Stress response proteins such as heat shock proteins and chaperones are some of the proteins that undergo changes in levels of expression and/or changes in cellular localization from the cytosol to the cell surface or the secretome, making them potential immunogens for vaccine development. Herein we highlight literature showing that intracellular chaperone proteins GroEL and DnaK, which were originally identified as playing a role in protein folding, are relocated to the cell surface or are secreted during invasion and therefore may be recognized by the host immune system as antigens. In addition, we highlight literature showcasing the immunomodulation effects these proteins can have on the immune system, also making them potential adjuvants or immunotherapeutics.
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FUJII, Honoka, Asuka TADA, Sachiko HORIE, Shiro MORI, and Tetsuya KODAMA. "Development of drug delivery system using lymphatic network." Proceedings of Mechanical Engineering Congress, Japan 2016 (2016): J2410104. http://dx.doi.org/10.1299/jsmemecj.2016.j2410104.
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HIRNLE, P. "Liposomes for Drug Targeting in the Lymphatic System." Hybridoma 16, no. 1 (February 1997): 127–32. http://dx.doi.org/10.1089/hyb.1997.16.127.
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KATO, Shigeki, Sachiko HORIE, Takuma SATO, and Tetsuya KODAMA. "7E36 Drug Delivery System for the Lymphatic Metastases." Proceedings of the Bioengineering Conference Annual Meeting of BED/JSME 2012.24 (2012): _7E36–1_—_7E36–2_. http://dx.doi.org/10.1299/jsmebio.2012.24._7e36-1_.
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Begum, Kousar, Dr B. Chandra Sekhara Rao, and Nukala Umasri. "Novel Drug Carriers to Target Lymphatic System - A Review." International Journal of Trend in Scientific Research and Development Volume-2, Issue-3 (April 30, 2018): 1402–12. http://dx.doi.org/10.31142/ijtsrd11247.
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MISHRA, Radhika, Ariunbunyan SUKHBAATAR, Shiro MORI, and Tetsuya KODAMA. "Optimal Osmotic Pressure for a Lymphatic Drug Delivery System." Proceedings of the Bioengineering Conference Annual Meeting of BED/JSME 2019.32 (2019): 2E31. http://dx.doi.org/10.1299/jsmebio.2019.32.2e31.
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Yang, Feng, De Liang Fu, Jiang Long, and Quan Xing Ni. "Magnetic lymphatic targeting drug delivery system using carbon nanotubes." Medical Hypotheses 70, no. 4 (January 2008): 765–67. http://dx.doi.org/10.1016/j.mehy.2007.07.045.
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Banda, Srikanth. "Tumor Biology; Usefulness of Thermosensitive and pH Sensitive Polymeric Nanoparticles for Tumor Targeting: A Review." Journal of Drug Delivery and Therapeutics 12, no. 4 (July 15, 2022): 141–53. http://dx.doi.org/10.22270/jddt.v12i4.5420.
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Polymeric nanoparticles (PNPs) have attracted the interest of many scientists and have been utilized in an increasing number of fields during the last two decades. The conventional chemotherapeutic agents have poor pharmacokinetic parameters such as non-specific distribution of drugs, the lack of drug specific affinity towards a pathological site, and thus necessitating large dose of a drug to achieve high local concentration in the body leading to systemic toxicity associated with serious side effects. A thorough and precise understanding of tumor microenvironment such as angiogenesis, tumor pH, enhanced permeation and retention (EPR) effect, abnormal lymphatics, multidrug resistance (MDR) and high interstitial fluid pressure, allows designing drug delivery systems that specifically target anti-cancer drugs to tumors. An attempt has been made in this article to highlight the temperature and pH sensitive PNPs, and PNPs with dual and double response to both temperature and pH that have a distinct capacity to target tumors with limited effect on healthy tissues. The stimuli responsive nanoparticles are classified based on their mechanism of response to temperature and pH. Structure of the polymer, methods of drug loading, and characterization of PNPs are elucidated.
Keywords: Polymeric nanoparticles; pH sensitive polymers; Thermosensitive polymers; Tumor microenvironment; Multidrug resistance; Drug loading.
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Yana, I. Gusti Agung Ari Kusuma. "Systematic Review: Comparison of triple drug therapy versus double drug therapy for Lymphatic Filariasis." Medical and Health Science Journal 5, no. 1 (February 28, 2021): 34–45. http://dx.doi.org/10.33086/mhsj.v5i1.1878.
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Background: Lymphatic filariasis is a parasitic infection caused by nematodes such as filaria Wuchereria bancrofti, Brugia malayi, and Brugia timori. These parasites can be transmitted through mosquito bites such as several species of mosquitoes, particularly Anopheles, Aedes, Culex, and Mansonia with geographical variations in the dominant vector identity. The main strategy used consists of community-wide mass drug administration (MDA) for the entire population at risk to stop disease transmission and prevent infectious morbidity. WHO recommends the use of annual medication in combination with the triple drug ivermectin therapy. Objective: To compare DEC and albendazole (IDA) versus the two drugs albendazole and diethycarbamazine or albendazole and ivermectin therapy. Methods: The literature search was carried out independently by the researcher using the Sciencedirect, Pubmed, and Cochrane online databases without limiting the type of study or the year of publication. The keywords used in this study were combined with the Boolean operator, namely "AND" namely ((((Lymphatic filariasis) AND (albendazole)) AND (diethylcarbamazine)) AND (ivermectin)) AND (compare). Results: Where triple drug therapy was significantly better in reducing and clearing microfilariae and worm nests in patients with lymphatic filariasis compared to two drug therapy alone. However, side effects occur more frequently in the combination of three therapies. The average side effects were low, such as headaches, joint pain, fatigue, and nausea. Conclusion: although it has relatively low side effects that occur in three drug combinations rather than two drug combination therapy, triple therapy combination therapy is more effective than two drug therapy in treating lymphatic filariasis disease.