氟维司群纳米聚合物胶束的制备与表征

Preparation and Characterization of Fulvestrant Polymeric Nanomicelles

目的:本文目的是制备氟维司群纳米聚合物胶束,并对其体外特性进行表征。方法:采用生物可降解材料甲氧基聚乙二醇-b-聚D,L-丙交酯(m PEG-b-PDLLA),并用固体分散法制备氟维司群聚合物胶束。利用透射电子显微镜与马尔文激光粒度测定仪分析胶束的形态与粒径。用X射线单晶体衍射仪定性测试胶束包封性。建立并验证氟维司群高效液相色谱(HPLC)分析方法,定量测定胶束载药量与包封率。采用透析袋法分析胶束体外释放情况。结果:氟维司群聚合物胶束形态圆整、分散均匀无粘连,粒径为89.97±4.33 nm,多分散指数为0.162±0.023,载药量与包封率达8.95%±0.86%与97.25%±0.86%。胶束释药具有明显的缓释特点。结论:成功制备氟维司群胶束并显著提高其水溶性,表现良好的缓释行为,能够开发为氟维司群的新型纳米制剂。

Objective： The purpose of this article is to prepare the fulvestrant nanomicelles（FNM） and investigate its physicochemical properties in vitro. Methods： FNM was made up of biodegradable m PEG-b-PDLLA copolymer and was prepared by solid dispersion method. The morphology and particle size of FNM was investigated by transmission electron microscopy（TEM） and malvern laser particle size analyzer. The characters were detected by and X-ray diffraction（XRD）. High-performance liquid chromatography（HPLC） analysis method was built and verified, using to measure drug loading and encapsulation efficiency. A dialysis method was used to determine the in vitro release behaviors of FNM. Results： The micelles are well dispersed as individual nanoscaled micelles with regularly spherical shape. The particle size and polydisperse index of FNM were 89.97±4.33 nm and 0.162±0.023, respectively. Drug loading and encapsulation efficiency reached 8.95 %±0.86 % and 97.25 %±0.86 %. FNM exhibited sustained-release action in vitro. Conclusions： The m PEG-b-PDLLA micelles loaded fulvestrant were successfully prepared. In vitro experiments showed that FNM significantly enhanced solubility of fulvestrant and released fulvestrant at a controlled rate. FNM should hold great potential for developing a novel formulation.