星点设计-效应面法优化壳聚糖温敏凝胶的制备及缓释性考察

Study on preparation and sustained-release of chitosan thermosensitive hydrogel by central composite design and response surface methodology

目的:通过壳聚糖/β-甘油磷酸钠(chitosan/β-glycerophosphate,CS/β-GP)温敏凝胶制备工艺的优化,为缓释载体的研究提供基础。方法:通过考察壳聚糖的脱乙酰度(degree of deacetylation,DD)、壳聚糖质量、β-GP浓度和pH,选取β-GP浓度和pH为星点设计考察因素,胶凝时间为考察指标,对结果进行多元线性和多项式拟合,效应面法优化工艺,并以神经生长因子(β-nerve growth fator,β-NGF)为模型药物,考察CS/β-GP温敏凝胶的缓释性,初步探讨其释药模型。结果:根据复相关系数可知,因素与指标之间的最佳拟合方程为三次多项式,最优工艺:β-GP浓度为511.51 mg·mL-1,pH为7.08,胶凝时间为6.23 min。且释药行为接近Weibull模型。结论:星点设计-效应面优化的CS/β-GP温敏凝胶工艺,具有胶凝时间短和缓释性好等优点,可满足植入给药的要求。

Objective：To optimize the preparation process of chitosan/β-glycerophosphate（CS/β-GP）thermosensitive hydrogel and lay a foundation for further research of sustained-release delivery system. Methods：By examining the degree of deacetylation（DD）of chitosan,the quality of chitosan,β-GP concentration and pH,β-GP concentration and pH were selected as investigation factors. By taking gelling time as an indicator,the experiment results were fitted with multiple linear or polynomial equations, and the process was optimize by response surface methodology. The sustained-release property of CS/β-GP temperature-sensitive gel was studied by using nerve growth factor（β-NGF）as a model drug,and its release model was explored. Results：Cubic polynomial equation fitted the correlation between the factors and indicators the best. The optimum preparation conditions were as follows： concentration of β-GP was 511.51 mg？mL-1,pH was 7.08, gel time was 6.23 min. The release behavior was close to the Weibull model. Conclusion：The CS/β-GP temperature sensitive gel optimized by central composite design-response surface methodology has the advantages of short gel time and sustained-release property, which meets the requirements of implantable drug delivery system.