以具有升温自固化特性的壳聚糖季铵盐/甘油磷酸钠混合溶液为水相，利用快速膜乳化与热固化法制备了粒径均一、pH敏感的壳聚糖季铵盐凝胶微球，考察了跨膜压力、水油相组成、水油相体积比及微孔膜孔径等对微球粒径、结构和药物包埋率的影响. 结果表明，得到粒径698±57.33, 1145±71.48, 2021±53.63及3984±191.72 nm、粒径分布窄(多分散系数<0.1)、药物包埋率高达75.49%±2.62%的凝胶微球. 所制微球生物相容性好，有明显的pH敏感性，中性和碱性环境下结构稳定，药物缓释，pH=7.4时24 h内药物累计释放率为34.6%；酸性环境下微球崩解，药物快速释放，pH=5.5时1 h内药物累计释放率高达79.6%.

N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC) hydrogel microspheres were prepared by premix membrane emulsification and thermal gelation methods, using HTCC/a-b-glycerophosphate mixed system with the property of thermal gelation as water phase. The effects of preparation conditions on size distribution, structure and drug encapsulation efficiency of microspheres, including transmembrane pressure, formulation of water phase and oil phase, volume ratio of water to oil phase and pore size of microporous membrane, were examined. After optimization, uniform-sized microspheres (polydispersity, PDI<0.1) with different sizes and high drug encapsulation efficiency (75.49%±2.62%) were obtained. The cytotoxicity and pH-sensitivity of as-obtained hydrogel microspheres were evaluated in comparison with the microspheres prepared by traditional method. The results showed that the as-obtained hydrogel microspheres possessed good biocompatibility and outstanding pH-sensitivity, and remained stable in neutral/alkalescent media and released drug in a relatively slow manner, with the drug cumulative release rate of 34.6% at 24 h in buffer solution at pH=7.4. While the hydrogel microspheres collapsed in acidic solution and led to a repaid drug release, and the cumulative release rate reached up to 79.6% in 1 h in buffer solution at pH=5.5.