Preparation and characterization of potential doxorubicin-loaded mixed micelles formed from vitamin E containing graft copolymers and PEG-b-PLA diblock copolymers

Abstract

In this study, mixed micelles formed from the biocompatible diblock copolymer methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (mPEG-b-PLA) and the vitamin E containing graft copolymer poly(hydroxypropyl methacrylamide)-g-α-tocopheryl succinate (PHPMA-g-α-TOS) were investigated to encapsulate anticancer drug doxorubicin (Dox) for evaluating anticancer capacity. Various graft and diblock copolymers were synthesized and characterized. Mixed micelles with optimal size and size distribution were successfully obtained from a fixed chain length and composition of graft and diblock copolymers. Dox was then loaded in the mixed micelles and the micelles demonstrated an acid-induced rapidly drug release behavior. The mPEG-b-PLA in mixed micelles not only exhibited an excellent anti-protein adsorption ability, but also accelerated α-TOS cleaved from graft copolymers and released from mixed micelles. From the cytotoxicity test, mixed micelles presented low risk to L929 normal cells but high toxicity to HCT116 colon cancer cells. An internalization study indicated that mixed micelles were accumulated more in HCT116 cells than micelles prepared from graft copolymers alone because mixed micelles had better stability in a serum medium. An ex vivo study also showed that mixed micelles could largely accumulate in the tumor. Based on these results, this mixed micelle system has great potential as a Dox-loaded carrier for use in cancer chemotherapy.