Effective loading and controlled release of camptothecin by O-carboxymethylchitosan aggregates

Increasing the solubility in aqueous environment while alleviating the toxicity of the delivery system at the same time are the vital challenges related to the administration of the antitumor drugs. In the present paper we describe a novel drug delivery system for the well known anticancer drug, camptothecin (CPT). This system is the aggregates of O-carboxymethylchitosan (OCMCS), which is a kind of biocompatible and amphiphilic chitosan derivative. The amount of drug loaded was examined by stead-state fluorescence. The release behaviors of CPT from this proposed controlled release system in PBS solution at 37 °C were studied by UV spectroscopy. The antiproliferative activity of cancer cell was evaluated using MTS assay. The results demonstrate that not only the aggregates but also the unimers of OCMCS can help to enhance the solubility of CPT. After CPT is loaded in OCMCS, the release of CPT is significantly sustained, which is caused by the interactions between OCMCS and lipophilic CPT. In vitro cancer antiproliferative activity test further confirms the slow release of CPT from OCMCS-drug system. The result of OCMCS unimers showing as good drug-loading and controlled release capability as its aggregates indicates that this novel release system can solve the commonly existing problem of unavailability of micelles assembled from amphiphilic copolymer in the significant dilution accompanying IV injection. These findings propose a new concept of a localized drug delivery.