去氢骆驼蓬碱聚合物胶束的制备工艺优化及体外释放的研究

目的：研究星点设计-响应面法优化去氢骆驼蓬碱N-癸酰-N-三甲基壳聚糖胶束（harmine loaded N-Decanoate-N-trimethyl chitosan micelles,HM-De-TMC-MIC）的处方优化,并考察在不同介质中HM-De-TMC-MIC的体外释放。方法：以薄膜分散法制备HM-De-TMC-MIC;以粒径、多分散系数、包封率和载药量为指标,通过单因素考察和星点设计-响应面法综合考察药物与载体质量比和复水体积对HM-De-TMC-MIC的影响,并遴选其最优处方。在不同pH的释放介质中,分别考察HM-De-TMC-MIC和HM的体外释放。结果：筛优处方药物与载体质量比为3.6∶10,复溶水体积为6 mL;以最优处方制备的HM-De-TMC-MIC粒径为（148.2±5.0）nm,多分散系数为0.198±0.045,包封率（89.80±0.19）%,载药量（22.79±0.05）%,形态圆整。体外释放试验结果表明,HM-De-TMC-MIC的释放曲线遵循Higuchi方程,与HM溶液相比其释放较为缓慢,并呈现pH敏感释药行为。结论：以星点设计-响应面法优化的HM-De-TMC-MIC具有较好包封率和载药量,粒径分布均匀,具有明显的缓释性。

Study on Optimized Formulation and Release in vitro of Harmine Loaded Micelles

Objective：To optimize the formulation of harmine loaded N-decanoate-N-trimethyl chitosan micelles with central composite design and response surface methodology and to study the release of harmine loaded micelles indifferent media in vitro. Methods： HM-De-TMC-MIC were prepared by the film dispersion method. Particle size, polydispersity, encapsulation efficiency and drug loading were selected as indexes, and the effects of the influence factors including drug to carrier weight ratio, rehydration volume were investigated by using central composite design and response surthce methodology and the optimal formulation was got. The release of HM from HM-De-TMC-MIC and HM solution in vitro was studied in different release media with different pH. Results： The optimal formulation got in the study was the drug to carrier weight ratio of 3.6：10 and rehydration volume of 6 mL. Under the optimal conditions, the obtained HM-De-TMC-MIC had a rounded shape with particle size of （148.2±5.0） nm, polydispersity of 0.198±0.045, encapsulation efficiency of （89.80±0.19）% and drug loading of （22.79±0.05）%. It was suggested by the release results in vitro that the dissolution curve of drug-loaded micelles release fitted well with Higuchi function. Compared with HM solution, HM loaded micelles way released relatively slower, and drug released with pH-sensitivity was demonstrated. Conclusions： In the study, with central composite design and response surface methodology, HM-De-TMC-MIC formulated with the optimal formulation had a medium particle size, a higher encapsulation efficiency and drug loading. And the sustained-release efficacy of HM-De-TMC-MIC was presented in vitro release.