Synthesis of Biodegradable Chitosan-Poly(D,L-Lactide) Hybrid Amphiphiles via Ring Opening Graft Polymerization for Efficient Gene Carrier

Biodegradable chitosan-graft-poly(_D,L-lactide) (CHI-PLA) have been prepared by in situ ring-opening polymerization of _DL-lactide (LA) grafting from chitosan. The chemical structure and physical properties of these chitosan derivatives were characterized by FTIR, ¹H-NMR, TGA and XRD. Formation and characteristics of polymeric micelles based on these chitosan derivatives were studied by fluorescence spectroscopy and dynamic light scattering (DLS). The critical micelle concentration (CMC) in water varied from 0.048 to 0.021 mg/mL as PLA grafting percentage (GP) increased from 92% to 132%. The mean diameters of CHI-PLA micelles have been readily tuned by controlling GP and the pH of micelles solution. The quasi-spherical micelles were observed by transmission electron microscopy (TEM). In particular, complexes formed by CHI-PLA micelles and plasmid DNA were investigated by agarose gel electrophoresis. Compared to chitosan, it could exhibit enhanced transfection efficiency in some cases and lower cell toxicity, as confirmed by in vitro transfection and cytotoxicity assay in L929 cell lines. These results indicated that CHI-PLA may be used as a new nonviral gene delivery vector for future gene therapy applications.