摘要
目的以聚乙二醇单甲醚-聚乳酸(m PEG-PLA)嵌段共聚物为载体材料,制备白藜芦醇载药胶束,应用单因素试验和星点设计-效应面法优化胶束的处方与制备工艺,并对载药胶束的理化性质进行评价。方法采用薄膜分散法制备白藜芦醇载药胶束,以透光率、载药量和包封率为评价指标,应用单因素试验和星点设计-效应面法优化胶束的处方与制备工艺,对结果进行多元线性回归及二项式拟合,预测较优的参数。应用透射电镜观察载药胶束的外观形态,动态光散射法测定其粒径、粒径分布及Zeta电位,差示扫描量热法表征白藜芦醇在载体中的分散状态,透析法测定载药胶束的体外释放行为。结果在优化条件下制备的载药胶束透光率为(93.23±0.72)%,载药量质量分数为(6.46±0.13)%,包封率为(83.7±0.03)%,与预测值偏差较小。载药胶束外形呈圆形或椭圆形,粒径分布均匀,平均粒径为(15.73±0.43)nm,Zeta电位为-(2.52±0.21)m V。DSC结果表明药物以分子或无定型态分散于嵌段共聚物载体中。与药物溶液相比,白藜芦醇载药胶束具有明显的缓释特征。结论单因素试验联合星点设计-效应面法可有效优化白藜芦醇载药胶束处方与制备工艺,白藜芦醇载药胶束粒径较小且均匀,载药量和包封率均较好。
Objective To optimize the formulation and preparation technology and to evaluate the physical and chemical properties of resveratrol（RES） loaded micelles.Methods Resveratrol-loaded micelles were prepared by film dispersion method.Single-factor experiment combined with central composite design-response surface methodology were applied to optimize the micelle formulation and preparation process with light transmittance,drug loading content and entrapment efficiency as indexes.Data were simulated using multilinear regression and second-order polynomial equation.The optimum formulation and preparation parameters were predicted by response surface method.Transmission electron microscopy（TEM） was employed to study the shape.Dynamic light scattering was used to study the particle size,particle size distribution and electric potential.Differential scanning calorimetry（DSC） confirmed the dispersed state of RES in block copolymer carriers.Dialysis method was developed for the determination of RES-loaded micelles in vitro release.Results The micelles prepared according to the optimized results showed light transmittance closing to93.23%（w）,the drug loading content of 6.46%（w） and entrapment efficiency of 83.70%,respectively.In the optimized formulation,the shape of RES loaded micelle was round or ellipsoidal with the particle size of（15.73 ± 0.43） nm,Zeta potential was-（2.52 ± 0.21） m V.DSC showed that the drug was dispersed in the block copolymer carriers of molecular state or non-crystalline.The release of the micelle and the drug solution were investigated.In vitro release results showed that RES-loaded micelles have obvious sustained release characteristics compared with the drug solution.Conclusions Single factor experiments combined with central composite design-response surface methodology are applicable for the formulation and preparation optimization of resveratrol micelles.RES-loaded micelles have small and uniform particle size.
出处
《沈阳药科大学学报》
CAS
CSCD
北大核心
2014年第12期927-934,1002,共9页
Journal of Shenyang Pharmaceutical University
基金
国家自然科学基金资助项目(81273448)
关键词
白藜芦醇
胶束
单因素
星点设计
效应面
resveratrol
micelle
single-factor
central composite design
response surface
