目的 以聚乙二醇-聚乳酸羟基乙酸共聚物（polyethylene glycol-polylactic acid-glycolic acid copolymer，mPEG-PLGA）为载体，探究积雪草苷mPEG-PLGA微球的最佳制备工艺。方法 首先从微球固化温度、乳化剂PVA质量浓度、搅拌速度、水油比以及mPEG-PLGA质量浓度中，筛选出影响积雪草苷微球制备的关键工艺参数，随后采用Box-Behnken设计-响应面法（Box-Behnken design-response surface methodology，BBD-RSM）实验进一步优化载药微球的制备条件，并对该微球形态、粒径分布、载药量、包封率、体外释放行为以及生物相容性进行综合评价。结果 固化温度、搅拌速度、乳化剂PVA与mPEG-PLGA质量浓度及水油比均影响微球包封率与形态。其中，固化温度与mPEG-PLGA质量浓度影响较大，固化温度过高或过低均降低微球包封率；mPEG-PLGA质量浓度增加可提高包封率，但过高却导致微球粘连与粒径增大。优化的条件为40 ℃、1 800 r/min、适量乳化剂PVA与mPEG-PLGA。选取mPEG-PLGA质量浓度、水油比和乳化剂PVA质量浓度作为考察因素，进行3因素3水平BBD实验设计，得到的积雪草苷mPEG-PLGA微球的最佳制备工艺为mPEG-PLGA质量浓度123.8 g/L、PVA质量浓度9.8 g/L，水油比12.7∶1。制备的积雪草苷微球粒径均匀，为（58.97.90±4.44）μm，载药量为（8.43±0.16）%，包封率达（62.66±0.84）%，在96 h内以稳定速度释放约80%的积雪草苷，与L929细胞共培养72 h后仍有高于90%的存活率。结论 成功制备积雪草苷mPEG-PLGA微球，所得微球粒径均匀、包封率与载药量较高，可实现药物缓释，并具有良好的生物相容性。该体系利用mPEG-PLGA的亲水性改善了药物稳定性与释放行为，为积雪草苷的高效递送提供了新策略。

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.

R283.6

湖北省自然科学基金资助项目（2025AFD706）