CI-921混合胶束的制备及透析拟合法测定胶束的包封率

Preparation of CI-921 mixed micelles and determination of its entrapment efficiency by method of dialysis and fitting

研制CI-921混合胶束（CI-Micelles），建立CI-Micelles包封率的测定方法，并对胶柬进行处方优化和体外表征。采用薄膜分散法制备CI-Micelles，通过透析法分离CI-Micelles的游离药物和载药胶柬，测定药物含量，得到包封率和载药量的测定值，利用方程拟合法推算出CI-Micelles包封率和载药量的真实值。考察聚合物的总量、两种聚合物用量的比例和水合介质的种类对胶束粒径分布、包封率和载药量的影响；考察载药胶束4℃下6d内的放置稳定性。结果表明，以总聚合物浓度为72ms／mL，PluronicF127与Solutol HS15质量之比为1：2，5％葡萄糖溶液为水合介质时制备的CI-Micelles具有最佳的包封率（〉90％）和粒径分布（17-25nm，分布系数〈0．210），在4℃下放置6d，包封率及粒径均无显著变化。本实验所建立的新型包封率的测定方法——透析拟合法可以用来考察难以达到漏槽条件的弱碱性药物小粒径胶束的包封率。利用混合配比的聚合物材料Pluronic F127和Solutol HS15制备的CI-Micelles粒径分布均匀，包封率和载药量高，稳定性较好。

The aim of this research were to prepare CI-921 mixed micelles （ CI-Micelles）, to establish a method for determining the entrapment efficiency of CI-Micelles, to optimize the formulation and to evaluate their in vitro properties. CI-Micelles were prepared by film dispersion. Dialysis and fitting were used to calculate true entrap- ment efficiency （EE） and drug loading （DL） of CI-Micelles. The influences of polymer concentration, polymer radio and hydrating media on the entrapment efficiency, drug loading and particle-size were investigated. The stability at 4℃ in 6 days was evaluated. The optimal formulation of CI-921-Micelles consisting of polymer con- centration of 72 mg/mL, a mass radio of Pluronic F127/Solutol HS15 at mass ratio of 1 ： 2 and 5% glucose solu- tion as hydrating medium, showed a EE of more than 90%, and mean particle-size of 17-25 nm and PDI 〈 0. 210. There were no significant changes to CI-Mieelles in EE and particle-size after treatment at 4℃ for6 days. The applied method of dialysis and fitting could be used to determine EE for micelles loaded with weakly basic drug which was difficult to meet sink conditions. Adjustment of the mass radio of Pluronic F127 to Solutol HS15 had resulted in uniform particle size distribution, high entrapment efficiency and drug loading capacity and better stability of CI-Micelles.