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过程工程学报 ›› 2015, Vol. 15 ›› Issue (3): 473-481.DOI: 10.12034/j.issn.1009-606X.215147

• 生化工程专栏 • 上一篇    下一篇

快速膜乳化与热固化法制备粒径均一的pH敏感壳聚糖季铵盐凝胶微球

刘艳 王月琦 范清泽 吴有斌 吴颉 马光辉   

  1. 中国科学院大学 中国科学院大学 中国科学院大学 中国科学院大学 国家生化工程技术研究中心 中国科学院过程工程研究所生化工程国家重点实验室
  • 收稿日期:2015-03-04 修回日期:2015-04-29 出版日期:2015-06-20 发布日期:2015-06-20
  • 通讯作者: 刘艳

Preparation of Uniform-sized pH-sensitive HTCC Hydrogel Microspheres by Premix Membrane Emulsification and Thermal Gelation

LIU Yan WANG Yue-qi FAN Qing-ze WU You-bin WU Jie MA Guang-hui   

  1. University of Chinese Academy of Sciences University of Chinese Academy of Sciences University of Chinese Academy of Sciences University of Chinese Academy of Sciences National Engineering Research Center for Biotechnology State Key Lab. Biochem. Eng., Inst. Process Eng., Chinese Academy of Sciences
  • Received:2015-03-04 Revised:2015-04-29 Online:2015-06-20 Published:2015-06-20
  • Contact: LIU Yan

摘要: 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%.

关键词: 快速膜乳化, 热固化, 壳聚糖季铵盐凝胶微球, 粒径均一, pH敏感性, 药物释放

Abstract: 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.

Key words: premix membrane emulsification, hermal gelation, HTCC hydrogel microspheres, size uniformity, pH-sensitivity, drug release

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