Antibacterial Activity and Cytotoxicity of Betainated Oligochitosane Derivatives

Insolubility of chitosan and oligochitosan in aqueous media above pH 6.2-6.5 and the resulting decreased penetration thorough mucosa restricts significantly their application in biomedical compositions. To create non-cytotoxic chitosan derivatives with a high antibacterial activity in weakly alkaline physiological media, alkali-soluble derivatives of oligochitosan and low-molecular weight chitosan were synthesized by coupling a betaine substituent to the nitrogen atom of glucosamine units. Comparative studies of the pH range of the solubility of these derivatives depending on the chain length and modification degree of oligochitosan with M-w = 9.7 +/- 1.7 kDa were carried out. It was found that 12 mol % of betaine substituents was the optimal modification degree ensuring the existence of a single-phase solution of modified oligochitosan (M-w= 2-10 kDa) within the entire pH range. Investigation of the antibacterial activity of betaine derivatives against gram-positive (S. aureus) and gram-negative (E. coli) bacteria revealed their high antibacterial effect in both weakly acidic and weakly alkaline environments. Betaine derivatives were found to be nottoxic towards cow lung epithelial cells (LEC) at concentrations below 2.5 mg/mL. The results obtained seem promising for the application of these derivatives in biomedical compositions.