Objective This study aimed to investigate the optimal preparation process for asiaticoside microspheres using polyethylene glycol-polylactic acid-glycolic acid copolymer (mPEG-PLGA) as the carrier. Methods Key process parameters affecting microsphere preparation were first screened from factors including curing temperature, emulsifier PVA concentration, stirring speed, water-to-oil ratio, and mPEG-PLGA concentration. Subsequently, a Box-Behnken design-response surface methodology (BBD-RSM) experiment was employed to further optimize the preparation conditions for the drug-loaded microspheres. Their morphology, particle size distribution, drug loading, encapsulation efficiency, in vitro release behavior, and biocompatibility were comprehensively evaluated. Results Curing temperature, stirring speed, emulsifier PVA and mPEG-PLGA concentrations, and water-to-oil ratio all influenced the encapsulation efficiency and morphology of the microspheres. Among them, curing temperature and mPEG-PLGA concentration had a greater impact: both excessively high and low curing temperatures reduced encapsulation efficiency; increasing mPEG-PLGA concentration improved encapsulation efficiency, but excessively high concentrations led to adhesion and increased particle size. The optimized conditions were 40 ℃, 1 800 r/min, with appropriate emulsifier PVA and mPEG-PLGA concentrations. Using mPEG-PLGA concentration, water-to-oil ratio, and emulsifier PVA concentration as investigation factors in a 3-factor, 3-level BBD experimental design, the optimal preparation process for asiaticoside mPEG-PLGA microspheres was determined as: mPEG-PLGA concentration 123.8 g/L, PVA mass concentration 9.8 g/L, and water-to-oil ratio 12.7∶1. The resulting microspheres had uniform particle size (58.97 ± 4.44) μm, a drug loading of (8.43 ± 0.16)%, and an encapsulation efficiency of (62.66 ± 0.84)%. They released approximately 80% of asiaticoside at a stable rate within 96 h, and maintained over 90% cell viability after 72 h of co-culture with L929 cells. Conclusion Asiaticoside-loaded mPEG-PLGA microspheres were successfully prepared. The obtained microspheres exhibit uniform particle size, relatively high encapsulation efficiency and drug loading, enable sustained drug release, and possess good biocompatibility. This system utilizes the hydrophilicity of mPEG-PLGA to improve drug stability and release behavior, providing a new strategy for the efficient delivery of asiaticoside.

asiaticoside  /  microspheres  /  mPEG-PLGA  /  response surface methodology  /  sustained release