Core-modified chitosan-based polymeric micelles for controlled release of doxorubicin

Amphiphilic stearic acid-grafted chitosan oligosaccharide (CSO-SA) micelles have been shown a good drug delivery system by incorporating hydrophobic drugs into the core of the micelles. One of the problems associated with the use of CSO-SA micelles is disassociation or the initial burst drug release during the dilution of drug delivery system by body fluid. Herein, the core of CSO-SA micelles was modified by the physical solubilization of stearic acid (SA) to reduce the burst drug release and enhance the physical stability of CSO-SA micelles. The CSO-SA micelles had 27.4 +/- 2.4 nm number average diameter, and indicated pH-sensitive properties. The micelle size and drug release rate from micelles increased with the decrease of pH value. After the incorporation of SA into CSO-SA micelles, the micelle size was increased, and the zeta potential was decreased. The extents of the increase in micelle size and the decrease of zeta potential related with the incorporated amount of SA. The in vitro drug release tests displayed the incorporation of SA into CSO-SA micelles could reduce the drug release from the micelles due to the enhanced hydrophobic interaction among SA, hydrophobic drug and hydrophobic segments of CSO-SA. (C) 2007 Elsevier B.V. All rights reserved.