Polisorbat 80 Kaplı, Kurkumin Ve Dosetaksel Yüklü Plga Nanopartiküler Sistemlerin Geliştirilmesi ve Beyin Tümörü Etkinliklerinin Değerlendirilmesi
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Seko, I. Synthesis, evaluation of in vitro and in vivo activities of curcumin and docetaxel loaded polysorbate 80 coated PLGA nanoparticulate systems. Hacettepe University Graduate School Health Sciences Institute, Pharmaceutical Technology Department, 2020. Delivery of drugs in Central Nervous System (CNS) is a major challenge for researchers. The blood-brain barrier (BBB) significantly inhibits the delivery of systemically administered therapeutic agents to the brain and limits the distribution and longevity of the locally distributed agents in brain extracellular matrix. Polysorbate 80 (Poly 80) coated PLGA nanoparticles (Poly 80-PLGA NPs) offer a promising solution to these problems. Following the intravenous injection drug loaded PLGA nanoparticles coated with Polysorbate 80 (Tween 80) provide effective brain transport method for antineoplastic drugs used in brain cancer treatment. Plant-derived curcumin, which is used in combination with antineoplastic drug with high side effects such as docetaxel, reduces side effects of cancer treatment by reducing dose of docetaxel. In this study, curcumin and docetaxel loaded PLGA nanoparticles are prepared using single emulsion method, the formulation is optimized using Box-Behnken design with 3 independent factors in 3 level, as follows; polymer concentration (X1), drug concentration (X2) and solvent/water ratio (X3) and as response NP size (Y1), drug loading ratio (Y2) and polydispersity (Y3). The prepared Poly 80-DTX-CCM- PLGA-NPs were characterized by particle size, polydispersity, zeta potential, drug loading ratio, TEM/SEM images and FTIR analysis. MTT test was performed on bEnd.3 endothelial and U87 glioma cells and IC 50 values were calculated for optimum formulation. In bEnd.3 and U87 cell lines it was observed that polysorbate 80 coated PLGA NPs showed an increased uptake compared to non-coated PLGA NPs. In vivo, CD1 mice injected with Poly 80-DTX-CCM-PLGA-NPs were shown to have been transported through BBB into the brain using the in vivo imaging system (IVIS).