Optimization of Chemical Synthesis for Production of a Skin‐Compatible and Scalable Copper Oxide Nanoparticles: A Promising and Safe Strategy for Healing of Non‐infected and Infected Wounds in Diabetes

The global challenge of wound healing is a critical public health concern, particularly for diabetes. The potential severe outcomes, such as gangrene or amputation, highlight the need for effective and timely treatment. The presence of resistant bacterial strains in diabetic wounds contributes to delayed wound healing, necessitating alternative antimicrobial agents. Copper oxide nanoparticles (CuO-NPs), have garnered recognition for their broad-spectrum antimicrobial activity, including efficacy against resistant bacterial strains, along with angiogenic properties. Given the challenges associated with green synthesis, The current study aimed to synthesize CuO-NPs using a scalable chemical method with minimal environmental impact. To the best of the author's knowledge, this is the first attempt to identify and optimize various factors in the synthesis process to produce a colloidal dispersion of CuO-NPs with properties compatible with rat skin, rendering them suitable for the management of diabetic wounds. The successful synthesis of CuO-NPs was validated with FTIR, DSC, XRD, and TEM. The antibacterial activity of CuO-NPs was also demonstrated against multidrug-resistant bacteria commonly found in diabetic wounds, including; Pseudomonas aeruginosa, Proteus vulgaris, Methicillin-resistant Staphylococcus aureus, and Staphylococcus aureus where MBC values recorded were, 500, 250, 750, and 225 µg/mL, respectively. Skin irritation test confirmed its compatibility with intact and abraded rat skin. CuO-NPs demonstrated complete wound healing for both non-infected and infected wounds in the diabetic animal model on day 15 and 18 of treatment, surpassing the wound contraction observed with the commercial wound dressing on day 30 and 33 (98% and 94% for non-infected and infected wounds, respectively). Therefore, CuO-NPs could be considered as a potential nano-medicinal agent for treating wounds in diabetes. However, it is crucial to conduct further studies focusing on its long-term toxicity and stability before advancing to pilot clinical studies. Additionally, the CuO-NPs produced in this study exhibited complete wound healing at a dose approximately 15 times lower than CuO-NPs with comparable characteristics synthesized by green method in a reference study. Thus, the current findings suggested that exploring various factors involved in the chemical synthesis of metal-based nanomaterials might represent another effective strategy for producing bio-compatible nanomaterials and facilitating their clinical translation.