Chitosan-graft-PAMAM loading nitric oxide for efficient antibacterial application

Abstract

Fabrication of nitric oxide (NO) donors with good biocompatibility and high NO loading efficiency for antibacterial applications remains a big challenge. In the present work, using low molecular weight chitosan (CS) with high water solubility as the backbone, we designed and synthesized a poly(amidoamine) (PAMAM) dendron-grafted CS using a fast and simple copper-catalyzed azide-alkyne cyclization reaction of azide-modified CS (CS-N3) and propargyl focal point PAMAM dendrons with the third generation. NO was loaded on CS-PAMAM via a reaction with its secondary amine groups, which resulted in the formation of CS-PAMAM/NONOate with a maximal NO loading amount of 1.7 μmoL/mg. The CS-PAMAM/NONOate showed significant antibacterial activity against both Gram-negative E. coli and Gram-positive S. aureus, where 2.5 mg of CS-PAMAM/NONOate showed an inhibition zone with a diameter of about 20 mm. Moreover, the CS-PAMAM/NONOate presented negligible toxicity on normal mouse embryonic fibroblast cells, suggesting excellent biocompatibility. These findings indicate that the prepared CS-PAMAM/NONOate is promising for use in wound dressing industry as wound healing and treatment of anti-bacterial infections.