pH-sensitive chitosan-derived nanoparticles as doxorubicin carriers for effective anti-tumor activity: preparation and in vitro evaluation

pH-sensitive self-aggregated nanoparticles (SNPs), based on amphiphilic deoxycholic acid (DOCA) modified carboxymethyl chitosan (DCMC), were prepared for delivery of the anticancer drug doxorubicin (DOX). DCMCs with different degrees of substitution (DS) of DOCA were initially synthesized and characterized. Based on self-aggregation, DCMC formed nanoparticles with size ranging from 87 to 174 nm. The critical aggregation concentration (CAC) decreased on increasing the DS of DOCA. Moreover, the DCMC SNPs showed an acidic pH-induced aggregation and deformation behavior. The DOX-loaded SNPs ([D]NP) exhibited a sustained drug release manner, which could be accelerated by an acidic pH, but delayed by a higher DS of DOCA. Antitumor efficacy results showed that [D]NP could suppress both sensitive and resistant MCF-7 cells effectively in a dose- and time-dependent manner. The enhanced cellular uptake and greater retention of [D]NP in drug-resistant cells, as evidenced by confocal microscopy and flow cytometry, contributed to a superior efficacy of [D]NP over free DOX. These results suggest the potential of DCMC SNPs as carriers for the hydrophobic drug DOX for effective cancer therapy against drug-resistant tumors. (C) 2012 Elsevier B.V. All rights reserved.