Preparation and pharmacodynamics of stearic acid and poly (lactic-co-glycolic acid) grafted chitosan oligosaccharide micelles for 10-hydroxycamptothecin.

Stearic acid (SA) and poly (lactic-co-glycolic acid) (PLGA) grafted chitosan oligosaccharide (SA-CSO-PLGA SCP) tripolymer was synthesized via the reaction between the carboxyl group of SA or PLGA with carboxylic side group, and the amine group of CSO in the presence of 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). The degrees of amino-substitution for SA and PLGA were assayed through 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) test and (13)C NMR spectrum, which were 8.15% and 5.82%, respectively; the critical micelle concentrations of SCP in PBS (pH 7.4) and deionized water (DI water) were about 34.9 and 14.5 microg/ml, respectively. Using 10-hydroxycamptothecin (HCPT) as a model drug, the drug-loaded micelles showed above 86% encapsulation efficiency, which not only enhanced the solubility of HCPT in aqueous medium markedly, but also protected the lactone ring of HCPT. Cellular uptakes of SCP micelles against A549, MCF-7 and HepG-2 tumor cells showed a faster cellular internalization. Comparing to the commercial HCPT injection, HCPT-loaded micelles showed higher cytotoxicities against A549, MCF-7 and HepG-2 cells. The increased folds were 22, 18 and 15, respectively. These results suggested the SCP could be applied as a carrier for hydrophobic drugs. 2010 Elsevier B.V. All rights reserved.