A comparison between optimized PLGA and CS-Alg-PLGA microspheres for long-lasting release of glatiramer acetate

JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY(2023)

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摘要
Glatiramer acetate (GA, Copaxone, COP, Copolymer-1) is one of the most prescribed drugs to treat relapsingremitting multiple sclerosis (RRMS). Herein, the formula of GA entrapped chitosan-alginate-poly (D, L-lacticco-glycolic acid) (CS-Alg-PLGA) microsphere has been studied as a novel carrier compared with conventional PLGA microsphere, pursuing long-lasting release to reduce the number of injections and minimize side effects. The preparation methods, including double-emulsion, homogenization, and solvent evaporation, were evaluated in preparing the GA/PLGA and GA/CS-Alg-PLGA microspheres. Dynamic light scattering (DLS), Field Emission Scanning Electron Microscopes (FE-SEM), Fourier transform infrared spectroscopy (FTIR), 1H nuclear magnetic resonance (1H NMR), and Thermogravimetric analysis (TGA) were performed for microspheres characterization. GA was successfully loaded within the PLGA and CS-Alg-PLGA microspheres with 96.93 +/- 0.9% and 97 +/- 0.86% encapsulation efficiency, with 96.2 +/- 1.24% and 86.91 +/- 1.18% in vitro release in 21 days, respectively. Moreover, the cell toxicity assay showed that the PLGA and CS-Alg-PLGA microspheres with and without the GA drug were nontoxic (at the range of this experiment) for Human Dermal Fibroblasts (HDF) cell line. In vitro release experiments exhibited long-lasting release of GA from both microspheres. Using the GA/PLGA and GA/ CS-Alg-PLGA microspheres in treating RRMS may improve the therapeutic efficiency and bioavailability of the drug.
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关键词
Multiple sclerosis,Glatiramer acetate,PLGA,Chitosan,Alginate,Microparticles
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