A series of novel chitosan derivatives: Synthesis, characterization and micellar solubilization of paclitaxel

A series of novel chitosan derivatives with octyl, sulfate and polyethylene glycol monomethyl ether (mPEG) groups as hydrophobic and hydrophilic moieties, respectively, were synthesized. These PEGylated amphiphilic chitosan derivatives were characterized with ¹H NMR, ¹³C NMR, FTIR and elemental analysis. And their physical properties were measured by wide angle X-ray diffraction (WAXD) and thermogravimetric analysis (TG). The critical micelle concentrations (CMCs) of the modified chitosans determined by using pyrene as a hydrophobic probe in fluorescence spectroscopy were found to be 0.011–0.079 mg/ml, and the log CMC was linearly relative to four structure parameters, that is the degree of substitution (DS) of chitosan unit, sulfate group, PEG unit and octyl group by mole per kilogram. Paclitaxel, a water-insoluble anticancer drug, was solubilized into the polymeric micelles formed by these derivatives utilizing physical entrapment method, with micellar particle size around 100–130 nm, and the highest paclitaxel concentration of 3.94 mg/ml was found in N-mPEG-N-octyl-O-sulfate chitosan (mPEGOSC) micellar solution, which was much higher than that in water (less than 0.001 mg/ml). Therefore, N-mPEG-N-octyl-O-sulfate chitosan micelles may be useful as a prospective carrier for paclitaxel.