聚乙二醇化磷脂胶束的纳米结构与功能

Nanostructrue and Function of PEGylated Phospholipid Micelles Encapsulation Drugs

梁伟等采用一步自组装法制备粒径在20 nm左右、具有核-壳结构的聚乙二醇化磷脂(PEG-PE)胶束,药物装载后对胶束的粒径无明显影响,但显著提高了胶束的体内外稳定性,被装载的药物主要分布在胶束的核-壳界面处.研究表明药物的理化性质决定了其与载体之间的组装机制及体外药物释放的特性.在不影响细胞膜的完整性及通透性的情况下,PEG-PE胶束通过插膜提高了细胞膜的流动性,进而促进小分子药物的翻转过膜,增加药物的入胞量.与游离药物相比,装载化疗药的胶束可增强药物对肿瘤组织的渗透能力,显著抑制动物皮下移植瘤的生长,延长动物的生存时间.PEG-PE胶束还通过增加药物在淋巴组织中的分布,降低了动物转移模型中的淋巴转移,相应地减少了肿瘤的肺部转移.PEG-PE为美国食品药品管理局(FDA)批准的可用于人体的药物载体材料,具有良好的生物相容性与安全性.因此,PEG-PE胶束作为药物载体具有广阔的发展前景.

We developed one-step self-assembly method to prepare poly（ethylene glycol）-phosphatidylethanolamine （PEG-PE） micelles, which had core-shell structure and particle size at 20 nm. Drug-loaded PEG-PE micelles displayed better stability than empty micelles in vitro and in vivo because the drug/polymer interactions reinforced the micellular structure. Drugs distributed at the core-shell interface of PEG-PE micelles without changing micellar size. Our studies demonstrated that physico-chemical properties of drugs determined their self-assembly mechanism with polymers and the release profiles of drugs from micelles in vitro. Encapsulation of drugs in micelles increased their cellular accumulation due to the increased membrane fluidity caused by PEG-PE insertion, which did not affect cell membrane permeability and integrity. Compared to free drugs, anticancer drugs encapsulated into PEG-PE micelles demonstrated an increased antitumor efficiency in vivo and an extended life span of mice by EPR effect of PEG-PE micelles. On the other hand, PEG-PE micelles maintained higher drug concentrations in lymphatic systems, thus resulting in significantly antitumor effects for metastatic tumors with less lung metastasis. PEG-PE is an FDA-approved nonionic diblock copolymer with good biocompatibility and safety. As drug delivery systems, PEG-PE micelles has a wide developmental future.