论文部分内容阅读
Poly (D, L-lactic-co-glycolic acid) (PLGA) is being an increasing extensive material to apply in the long-acting drug delivery system.Currently the most adopted methods to prepare PLGA microparticles (PLGA-MPs) are emulsion solvent evaporation method and spray drying technology.However, the low encapsulation efficiency and process instability of protein/peptide drugs are the greatest challenges with these methods.The novel ultra-fine particle processing system (UPPS) is a proprietary technology developed by our group based on the disk rotation principle, which could prepare PLGA-MPs under mild conditions and ensure high encapsulation efficiency.The purpose of this study was to develop and validate exenatide-loaded PLGA-MPs (Ex-PLGA-MPs) used as a long-acting delivery system which prepared by UPPS.The characteristics of Ex-PLGA-MPs including morphology, particle size distribution, drug content, encapsulation efficiency and in vitro release were studied.The interactions between Ex and PLGA were investigated by Fourier transform infrared spectroscopy (FTIR) and circular dichroism spectrum (CD).Cytotoxicity of the Ex-PLGA-MPs was examined on A549 cells and the pharmacodynamics was evaluated in vivo in type 2 diabetes Sprague-Dawley (SD) rats.Ex-PLGA-MPs showed good uniformity of particle size, high encapsulation efficiency (90.16±3.52%), no obvious initial burst release,and stable sustained release for more than one month in vitro.FTIR and CD results indicated that there was non-reactive nature between PLGA and exenatide, and UPPS technology could effectively protect the bioactivities of exenatide.The cytotoxicity experiment of Ex-PLGA-MPs on A549 cells showed its good biocompatibility for injection.Meanwhile,the Ex-PLGA-MPs could effectively control the body growth rate and blood glucose in diabetes SD rats for at least three weeks after a single injection.The results suggested that UPPS could successfully improve encapsulation efficiency and effectively protect the activity of exenatide.Ex-PLGA-MPs may be used as a long-acting formulation applied in treatment type 2 diabetes.UPPS was proved to be a promising manufacture technology to prepare long-acting drug delivery system.