Hu Xiuli, Jing Xiabin
Chinese Academy of Sciences, Changchun Institute of Applied Chemistry, PR China.
Expert Opin Drug Deliv. 2009 Oct;6(10):1079-90. doi: 10.1517/17425240903158917.
The coupling of drugs to macromolecular carriers received an important impetus from Ringsdorf's notion of polymer-drug conjugates. Several water-soluble polymers, poly(ethylene glycol), poly[N-(2-hydroxypropyl) methacrylamide], poly(l-glutamic acid) and dextran, are studied intensively and have been utilized successfully in clinical research. The promising results arising from clinical trials with polymer-drug conjugates (e.g., paclitaxel, doxorubicin, camptothecins) have provided a firm foundation for other synthetic polymers, especially biodegradable polymers, used as drug delivery vehicles. This review discusses biodegradable polymeric micelles as an alternative drug-conjugate system. Particular focus is on A-B or B-A-B type biodegradable amphiphilic block copolymer such as polylactide, morpholine-2,5-dione derivatives and cyclic carbonates, which can form a core-shell micellar structure, with the hydrophobic drug-binding segment forming the hydrophobic core and the hydrophilic segment as a hydrated outer shell. Polymeric micelles can be designed to avoid uptake by cells of reticuloendothelial system and thus enhance their blood lifetime via the enhanced permeability and retention effect. Active tumor-targeting may be achieved by modifying the micelle surface with specific ligands. The potential application areas are discussed and future challenges are highlighted.
药物与大分子载体的偶联因林斯多夫提出的聚合物-药物缀合物概念而获得了重要推动。几种水溶性聚合物，如聚乙二醇、聚[N-(2-羟丙基)甲基丙烯酰胺]、聚(l-谷氨酸)和葡聚糖，得到了深入研究，并已成功应用于临床研究。聚合物-药物缀合物（如紫杉醇、阿霉素、喜树碱）临床试验所取得的令人鼓舞的结果，为用作药物递送载体的其他合成聚合物，尤其是可生物降解聚合物，奠定了坚实基础。本综述讨论了可生物降解聚合物胶束作为一种替代药物缀合物系统。特别关注的是A-B或B-A-B型可生物降解两亲性嵌段共聚物，如聚丙交酯、吗啉-2,5-二酮衍生物和环状碳酸酯，它们可形成核壳胶束结构，其中疏水性药物结合段形成疏水核心，亲水性段作为水合外壳。聚合物胶束可设计成避免被网状内皮系统的细胞摄取，从而通过增强的渗透和滞留效应延长其在血液中的存留时间。通过用特定配体修饰胶束表面可实现主动肿瘤靶向。文中讨论了潜在的应用领域，并强调了未来的挑战。
