Enhanced Cytotoxicity of Core Modified Chitosan Based Polymeric Micelles for Doxorubicin Delivery

In this study, the cytotoxicity of doxorubicin (DOX) loaded stearic acid grafted chitosan oligosaccharide (CSO-SA) micelles and its core modified drug delivery systems were investigated in vitro. The in vitro drug release experiments using cellular culture medium, Roswell Park Memorial Institute 1640 (RPMI-1640) medium as a dissolution medium confirmed that the DOX release from CSO-SA micelles was successfully delayed by the core modification of CSO-SA micelles with stearic acid (SA). The cell viability assay against A549 cells indicated the 50% inhibition concentration (IC50) Of blank CSO-SA micelles and the core modified CSO-SA micelles was 369 +/- 27 mu g/mL and 234 +/- 9 mu g/mL, respectively. The entrapment of DOX by CSO-SA micelles could decrease the IC50 of DOX from 3.5 to 1.9 mu g/mL, and a further reduction to 0.7 mu g/ml, could result by the core modification of CSO-SA micelles. The fluorescence image observations of DOX and DOX concentration measurements inside A549 cells demonstrated that the DOX concentration inside cells was increased by the entrapment of CSO-SA micelles, and further enhanced by the core modification of CSO-SA micelles. The results indicated that the CSO-SA micelles with modified cores could be useful as a drug delivery vehicle for cancer chemotherapy. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:704-712, 2009