Preparation and characteristics of stearic acid grafted chitosan oligosaccharide polymeric micelle containing 10-hydroxycamptothecin

Purpose: To prepare stearic acid grafted chitosan oligosaccharide (CSOS-SA) micelle loading 10-hydroxycamptothecin (HCPT), and
investigate the physicochemical properties and in vitro anti-tumor activity of the drug delivery system. Methods: CSOS-SA was synthesized by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated coupling reaction. The degree of substitution (DS) was determined by 2,4,6-trinitrobenzene sulfonic acid method (TNBS) and critical micelle concentration (CMC) was measured by fluorescence measurement using pyrene as a probe. The anti-tumor activity in vitro of HCPT loaded micelles and free HCPT was investigated by MTT method. Results: DS of CSOS-SA was 15.97% and CMC was 0.0085 mg/ml. Size of CSOS-SA micelles was about 30 nm and zeta potential was about 30 mV. The saturated solubility of HCPT was 1.01 µg/ml in distilled water under 37˚C, and it was enhanced markedly to be 18.92 µg/ml due to encapsulation of the micelles. The stability of HCPT in aqueous medium was also enhanced markedly after HCPT was loaded into the micelles. IC50 of HCPT loaded micelles and free HCPT were 0.052 and 4.76 μg/ml, respectively. Conclusions: The saturated solubility and stability of HCPT in distilled water were enhanced markedly when HCPT was encapsulated into micelles. Compared with free HCPT, the cytotoxicity of HCPT encapsulated into micelles was improved sharply, which contributed to the increased intracellular delivery of the drug and its stability in medium. The presented CSOS-SA micelles may be a promising carrier candidate for hydrophobic drug.

Keywords: Polymer micelles Solubilization Protection 10-Hydroxycamptothecin Cytotoxicity