Nitric oxide generating copper–chitosan particles for wound healing applications

BACKGROUND Nitric oxide (NO) is a signaling molecule that plays many roles during infection, inflammation, and wound healing processes. Due to the role of NO in wound repair, a novel NO generation system was developed based on copper–chitosan complexes that can be used for the topical generation of NO. Chitosan, a biocompatible polymer, chelates copper ions. Copper in the +1 state can reduce nitrite (NO 2 – ) and convert it into NO. With glucose, a reducing sugar, present in the system, Cu +2 can be returned to Cu +1 to complete the catalytic cycle. RESULTS Copper–chitosan milli‐ and micro‐sized particles were produced using microfluidic techniques. Copper–chitosan milli‐particles (Cu‐chito) did produce nitric oxide (NO). The maximum rates of NO production were ∼ 1.40 nmol min ‐1 g ‐1 (Cu‐chito) and 1.08 nmol min ‐1 g ‐1 (Cu‐chito + glucose). The milli‐particles were tested with ARPE‐19 cell lines in cell proliferation assays. Cu‐chito particle treatments with nitrite showed 130% more growth in comparison with chitosan milli‐particles not containing copper. Furthermore, Cu‐chito treatments of nitrite + glucose showed 152% more growth in comparison with control groups, and 118% in comparison with Cu‐chito with nitrite alone. The activity of intracellular NO target, matrix metalloproteinases (MMP‐2 and ‐9), were shown to increase by 60% after 48 h of Cu‐chito ± glucose treatments. CONCLUSION NO‐releasing copper–chitosan derivatives were produced, with proof of concept for nitric oxide release and positive effects on a cell culture model of wound healing. © 2018 Society of Chemical Industry