Combination Loading of Doxorubicin and Resveratrol in Polymeric Micelles for Increased Loading Efficiency and Efficacy.

Abstract

Combined loading of doxorubicin (DOX) and resveratrol (RSV) in polymeric micelles enabled an increased loading of DOX into a micellar drug delivery system. Herein, we report the coloading of DOX and RSV in amphiphilic diblock copolymer micelles of poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) and poly(ethylene glycol)-b-poly(γ-benzyl-ε-caprolactone) (PEG-b-PBCL) for which an increase in the loading efficiency and increased in vitro cytotoxicity was observed. The increased loading was attributed to the favorable interactions of DOX and RSV as well as to the interaction with benzyl substituents of PEG-b-PBCL diblock copolymer micelles. Combination loaded micelles made of PEG-b-PBCL diblock copolymer showed a dramatic improvement in DOX loading in comparison to DOX-only loaded PEG-b-PBCL with an increase in encapsulation efficiency of DOX from 31.0 to 87.7%. Combination loaded micelles also showed increased cytotoxicity to HeLa cells as compared to that of DOX-only loaded micelles. Optimization of the combination loading, size and morphology, drug release, and cellular studies is also reported here. Combination loading was shown to improve the loading capacity and efficiency of both systems and shows promise to improve loading of DOX in polymer micelle systems regardless of the polymer used.