Bioresorbable filomicelles for targeted delivery of betulin derivative – In vitro study

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.