Synthesis, Characterization, and Drug-Release Behavior of Amphiphilic Quaternary Ammonium Chitosan Derivatives

A new type of amphiphilic quaternary ammonium chitosan derivative, 2-N-carboxymethyl-6-O-diethylaminoethyl chitosan (DEAE-CMC), was synthesized through a two-step Schiff base reaction process and applied to drug delivery. In the first step, benzaldehyde was used as a protective agent for the incorporation of diethylaminoethyl groups to form the intermediate (6-O-diethylaminoethyl chitosan). On the other hand, NaBH4 was used as a reducing agent to reduce the Schiff base, which was generated by glyoxylic acid, for the further incorporation of carboxymethyl groups to produce DEAE-CMC. The structure, thermal properties, surface morphology, and diameter distribution of the resulting chitosan graft copolymers were characterized by Fourier transform infrared spectroscopy, H-1-NMR, thermogravimetric analysis, differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, and laser particle size analysis. Benefiting from the amphiphilic structure, DEAE-CMC was able to be formed into microspheres in aqueous solution with an average diameter of 4.52 +/- 1.21 m. An in vitro evaluation of these microspheres demonstrated their efficient controlled release behavior of a drug. The accumulated release ratio of vitamin B-12 loaded DEAE-CMC microspheres were up to 93%, and the duration was up to 15 h. The grafted polymers of DEAE-CMC were found to be blood-compatible, and no cytotoxic effect was shown in human SiHa cells in an MTT [3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyltetrazolium bromide] cytotoxicity assay. These results indicate that the DEAE-CMC microspheres could be used as safe, promising drug-delivery systems. (c) 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39890.