Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Curie-Sklodowska 34 St., 41-819 Zabrze, Poland.
Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Curie-Sklodowska 34 St., 41-819 Zabrze, Poland; School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland, Department of Biopharmacy, Jedności 8, Sosnowiec, Poland.
Int J Pharm. 2019 Feb 25;557:43-52. doi: 10.1016/j.ijpharm.2018.12.033. Epub 2018 Dec 18.
Filomicelles (worm-like micelles) possess high drug loading capacity and long circulation time in the bloodstream. A novel approach can be filomicelles with folic acid (FA) as a targeting moiety. Folate-drug delivery systems can target FA receptors (FAR) that are overexpressed in several human carcinomas, which can potentially maximize therapeutic efficacy while minimizing side effects. The aim of this study was to develop filomicelles from combination of poly(L-lactide)-Jeffamine-folic acid and poly(L-lactide)-poly(ethylene glycol) for delivery of betulin derivative. Phosphate derivative of betulin reveals high cytotoxicity against cancer cells, however its application is restricted due to poor solubility in water. Incorporation into hydrophobic core of micelles can effectively solubilize the drug. Three kinds of micelles were obtained with high drug loading capacity. Based on TEM analysis, the copolymers formed exclusively filomicelles or mixture of filomicelles and spherical micelles. All kinds of micelles provided release of betulin derivative for over 9 days and apart the very initial phase displayed similar release profile. The influence of PLA block on initial burst effect was revealed. The in vitro cytotoxicity of betulin derivative loaded micelles against FAR-positive HeLa cells was confirmed, which proves their usefulness for targeted delivery of cytostatic drug.
纤维胶束（蠕虫状胶束）在血液中具有高载药量和长循环时间。一种新方法可以将叶酸（FA）作为靶向部分的纤维胶束。叶酸-药物传递系统可以靶向在几种人类癌中过度表达的 FA 受体（FAR），这可以最大限度地提高治疗效果，同时最小化副作用。本研究的目的是开发聚（L-丙交酯）-Jeffamine-叶酸和聚（L-丙交酯）-聚（乙二醇）的组合纤维胶束，用于贝鲁汀衍生物的递药。贝鲁汀的磷酸盐衍生物对癌细胞具有高细胞毒性，但其应用受到限制，因为其在水中的溶解度差。将其掺入胶束的疏水核中可以有效地增溶药物。得到了三种载药能力高的胶束。基于 TEM 分析，共聚物仅形成纤维胶束或纤维胶束和球形胶束的混合物。所有类型的胶束均能在 9 天以上释放贝鲁汀衍生物，且除了初始阶段外，其释放曲线相似。揭示了 PLA 嵌段对初始突释效应的影响。证实了载有贝鲁汀衍生物的胶束对 FAR 阳性 HeLa 细胞的体外细胞毒性，这证明了它们在靶向递送细胞毒药物方面的有用性。
