伊曲康唑mPEG-PLA聚合物胶束的制备及理化性质

Preparation and physico-chemical properties of itraconazole polymeric micelles using mPEG-PLA as a drug carrier

研究以聚乙二醇单甲醚-聚丙交脂嵌段共聚物(mPEG-PLA)作为载体,制备伊曲康唑聚合物胶束(ITZ-PM)。以开环聚合法合成mPEG-PLA,以溶剂挥发-薄膜分散法制备ITZ-PM溶液,并将其冷冻干燥。分别使用HPLC、动态光散射法(DLS)、原子力显微镜(AFM)和差示扫描量热法(DSC)等手段对载药量、包封率、粒径与分布和胶束形态等进行表征,采用透析法考察ITZ-PM的体外释放,并对释放机制进行探讨。结果显示ITZ-PM载药量为3.82%,包封率为99.4%,平均粒径为37.8 nm,pH为4.48;DSC确证药物已被包封在胶束中;AFM显示胶束呈类球形;ITZ-PM较市售制剂有一定缓释作用,释药行为较为符合Peppas-Sahlin方程。研究结果表明mPEG-PLA能有效提高伊曲康唑的溶解度。

A formulation of itraconazole polymeric micelles was prepared using mPEG-PLA as the drug carrier. mPEG-PLA was synthesized by ring opening and polymerization reaction. ITZ-PM was prepared by solvent evaporation-film dispersion method. The drug-loading and entrapment efficiency were characterized by I-IPLC. The physico：ehemical properties of ITZ-PM was characterized by dynamic light scattering （ DLS）, atomic force microscopy （AFM） and differential scanning calorimeter （DSC）, respectively. The dialysis method was applied to investigate the release behavior of ITZ-PM in vitro, and the release mechanism was further discussed. Drug-loading and encapsulation efficiency of ITZ-PM were 3.82% and 99.4%, respectively; nanopartiele size was 37.8 nm, and pH was 4. 48. Itraeonazole was found to be encapsulated in the micelles rather than forming a physical mixture by DSC; ITZ-PM exhibited to be almost spherical in shape from the observation by AFM. It was proved that ITZ-PM had sustained-release effect in vitro which could be described by Peppas-Sahlin equation. Results showed that mPEG-PLA can obviously improve the solubility of itraconazole.