Engineering of peglayted camptothecin into core–shell nanomicelles for improving solubility, stability and combination delivery

Abstract

Camptothecin (CPT), a broad-spectrum anticancer drug, is limited in the extensive applications for its extremely hydrophobic property and low physiological stability in clinical use. In this study, prodrug of PEGylated CPT bioconjugate was synthesized to address the above critical issues. The as-designed amphiphilic conjugate could self-assemble into core–shell nanomicelles to enhance the solubility of the CPT and simultaneously improve the stability by encapsulating CPT in the micellar core. Furthermore, the core–shell structure of nanomicelles affords the capability of combination drug delivery by loading other hydrophobic drugs in the core. Doxorubicin (DOX) was chosen as model for combination delivery by physical encapsulation method. It is demonstrated that DOX could be efficiently loaded with controlled release kinetics. Cellular uptake experiments show that this micelle based drug delivery system is able to be efficiently uptaken by cells to achieve combination delivery. In vitro cytotoxicity of the CPT micelles and the DOX-loaded system are evaluated respectively through cell cytotoxicity against Hela cells, the results show an obviously enhanced cytotoxicity over free CPT while the DOX-loaded system exhibit more potent inhibition on cell proliferation ascribed to the combined effect of physically entrapped DOX and chemical conjugated CPT.