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 µg/mL and 234 ± 9 µg/mL, respectively. The entrapment of DOX by CSO‐SA micelles could decrease the IC50 of DOX from 3.5 to 1.9 µg/mL, and a further reduction to 0.7 µg/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. © 2008 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:704-712, 2009