Acid-sensitive chitosan-based nanocapsules for anticancer drug delivery

Abstract

Novel biodegradable chitosan-based nanocapsules with well-defined acid-sensitive structures were prepared by the synthesis of N-maleyl-functionalized chitosan (NCS), followed by interfacial cross-linking of NCS with a hydrolysable dithiol cross-linker via UV-induced thiol-ene reaction in oil-in-water miniemulsions. The morphology and the size distribution of the nanocapsules were characterized by TEM and DLS, respectively. The results revealed that they possessed compact and spherical morphology with nano-sizes, which can be tuned by varying surfactant concentration into the optimal size range for application as biomedical delivery scaffolds. In addition, in vitro drug release and degradation studies indicated that DOX-loaded nanocapsules displayed pH-dependent degradation behavior and faster DOX release at pH of 5.5 than pH of 7.4. Moreover, as compared with free DOX, they showed similar in vitro cytotoxicity against MCF-7 cells. Confocal imaging indicated that they could readily be uptaken by MCF-7 cells. Thus, these chitosan-based nanocapsules could serve as an effective and safe vehicle for the delivery of potent hydrophobic anti-cancer drug, especially DOX.