New water-soluble oxyamino chitosans as biocompatible vectors for efficacious anticancer therapy via co-delivery of gene and drug

Among the many non-viral gene delivery vectors, chitosan, being a polysaccharide of natural origin, has gained special importance. In this report, chitosan, CS has been solubilized in water by preparing its O-carboxymethyl derivative, CS(CH2COOH) with an optimum degree of carboxymethylation. This has been further derivatized to get the pyridine substituted product, (py)CS(CH2COOH) where the degree of pyridine substitution (47%) was optimised based on zeta potential measurements. The optimized formulation showed a high gene binding ability, forming nano-sized positively charged polyelectrolyte complexes with DNA. These polyplexes were stable to DNAse and physiological polyanions like heparin. They also exhibited minimal toxicity in vitro and showed transfection levels comparable to the commercial standard Lipofectamine 2000 and much higher than polyethyleneamine (MW 25 kDa). Additionally, in this study, a hitherto unknown oxyamine derivative of chitosan has been prepared by phthaloyl protection, tosylation...