载白藜芦醇泊洛沙姆403/407混合胶束的制备及其体外性质  

Optimization and in vitro characterization of resveratrol-loaded poloxamer 403/407 mixed micelles

作　　者：李金凤[1] 高明月[1] 王慧敏[1] 刘巧钰 毛世瑞[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《药学学报》2015年第8期1045-1051,共7页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81273446);高等学校博士点基金资助项目(20122134110005)

摘　　要：本文制备了载白藜芦醇的泊洛沙姆403/407混合聚合物胶束,并通过优化处方实现药物的高负载和缓慢释放。首先采用薄膜分散法制备混合胶束,并以包封产率、载药量和粒径为考察指标,通过星点设计效应面法优化处方。测定空白载体的临界胶束浓度,模拟生理条件下研究胶束的稀释稳定性,透析法考察胶束的体外释放行为。结果表明,实验所得最优处方的载药量和包封产率分别为11.78%和82.51%,粒子均一,平均粒径为24 nm。在混合胶束中,药物的溶解度为5.92 mg·m L-1,与药物本身溶解度相比,提高了约197倍。混合胶束具有很强的抗稀释能力,且白藜芦醇可从混合胶束中缓慢释放达20 h以上,其释放行为符合Higuchi方程。因此,该混合胶束体系不仅可以显著提高白藜芦醇的溶解度,还能实现药物的缓慢释放。The objectives of this study are to prepare resveratrol loaded mixed micelles composed of poloxamer 403 and poloxamer 407, and optimize the formulation in order to achieve higher drug solubility and sustained drug release. Firstly, a thin-film hydration method was utilized to prepare the micelles. By using drug-loading, encapsulation yield and particle size of the micelles as criteria, influence of three variables, namely poloxamer 407 mass fraction, amount of water and feeding of resveratrol, on the quality of the micelles was optimized with a central composite design method. Steady fluorescence measurement was carried out to evaluate the critical micelle concentration of the carriers. Micelle stability upon dilution with simulated gastric fluid and simulated intestinal fluid was investigated. The in vitro release of resveratrol from the mixed micelles was monitored by dialysis method. It was observed that the particle size of the optimized micelle formulation was 24 nm, with drug-loading 11.78%, and encapsulation yield 82.51%. The mixed micelles increased the solubility of resveratrol for about 197 times. Moreover, the mixed micelles had a low critical micelle concentration of 0.05 mg·mL^-1 in water and no apparent changes in particle size and drug content were observed upon micelles dilution, indicating improved kinetic stability. Resveratrol was released from the micelles in a controlled manner for over 20 h, and the release process can be well described by Higuchi equation. Therefore, resveratrol-loaded poloxamer 403/407 mixed micelles could improve the solubility of resveratrol significantly and sustained drug release behavior can be achieved.

关 键 词：泊洛沙姆403 泊洛沙姆407 白藜芦醇 胶束 

分 类 号：R943[医药卫生—药剂学]