姜黄素Pluronic F127载药胶束的制备及其胶束化行为的NMR分析

目的： 以姜黄素为模型药物，制备Pluronic F127聚合物的载药胶束并阐明Pluronic F127在水中的胶束化过程。方法： 采用HPLC测定姜黄素含量，流动相0.1%甲酸水溶液-甲醇（30:70），检测波长420 nm。采用薄膜水化法制备姜黄素Pluronic F127胶束，通过正交试验考察姜黄素-Pluronic F127质量比、水相用量、水相pH和水化时间对载药共聚物胶束包封率及载药量的影响。利用动态光散射法测定胶束粒径，动态透析法考察载药胶束的体外释放行为，并通过¹H-NMR分析Pluronic F127在水中的胶束化行为。结果： 优选的处方工艺为姜黄素-Pluronic F127（1:15），水相用量10 mL，水相pH 5.0，水化时间1.0 h。姜黄素Pluronic F127胶束的平均粒径约30 nm，平均包封率64.5%，平均载药量4.1%，体外释放符合Higuchi方程。在水中随着Pluronic F127质量浓度的增高，质子的NMR化学位移向高场移动且信号变宽。结论： Pluronic F127在水中已形成了可载药的疏水性胶束内核，Pluronic F127具有优良的载药及缓释能力。

Preparation of Curcumin-Loaded Pluronic F127 Micelles and NMR Analysis of Its Micellization Behavior

Objective: To prepare curcumin-loaded Pluronic F127 micelles and clarify micellization behavior of Pluronic F127 in water. Method: The content of curcumin was determined by HPLC with mobile phase of 0.1% formic acid solution-methanol(30:70) and detection wavelength of 420 nm.Curcumin-loaded Pluronic F127 micelles were prepared by thin-film hydration method and effects of curcumin-Pluronic F127 mass ratio,aqueous phase amount,pH of aqueous phase and hydration time on drug-loading coefficient and entrapment efficiency were investigated by orthogonal design.Particle size of micelles was determined by dynamic light scattering method. In vitro release profile of curcumin in micelles was investigated by dynamic dialysis method.¹H-NMR was performed to study micellization behavior of Pluronic F127 in water. Result: Optimized formulation process was as follows:curcumin-Pluronic F127(1:15),aqueous phase amount 10 mL,pH of aqueous phase 5.0 and hydration time 1.0 h. Average size of curcumin-loaded Pluronic F127 micelles was about 30 nm with average entrapment efficiency of 64.5% and average drug-loading coefficient of 4.1%. In vitro release data fitted well to Higuchi equation.¹H-NMR results demonstrated that chemical shift of Pluronic F127 upshifted and signals broadened with increasing of the concentration. Conclusion: Pluronic F127 has been formed hydrophobic micelles core for drug-loaded in water,thus showing excellent drug-loaded and release capability.