Searching for synergistic effects of low-molecular weight chitosan derivatives, chitosan and copper nanoparticles for wound healing ointment

Abstract

A high demand for modern wound healing drugs is associated with an increasing amount of injuries, chronic and diabetic ulcers, and wound infection resistance to antibiotics. The strategy for improving antibacterial capacity along with stimulation of wound reparation seems fruitful. Chitosan and copper have multifunctional properties, possessing both regenerative and antimicrobial action. The use of modified copper nanoparticles (NPs) of optimal size and phase content in combination with low molecular weight chitosan derivatives or chitosan NPs in the hydrophilic polymer composition with cellulose opens new horizons for wound management. The best synergistic composition for wound healing was a combination of 0.002% Cu1O x NPs and 0.05% N-sulfosuccinoyl-N-carboxymethyl chitosan. Such hydrogels increase the rate of wound closure (by 37%–39% as compared to gels containing individual components and by 65% in comparison with control), to provide effective angiogenesis, re-epithelisation, collagen deposition in the wound, antibacterial activity and cell biocompatibility. The high regenerative effectiveness of ointments with copper NPs at the initial stage of wound healing seems to be a result of activation of the signal rout of the regeneration process by copper, an increase of the NO level in the wound tissue was evidenced by EPR studies. This work proposes a new approach in the development of polyfunctional ointments with wound healing and antibacterial properties.