Wound Healing Activity of Iron Oxide Nanoparticles; Comparative In Vivo Study on Staphylococcus aureus-Infected and Non-Infected Wounds

Abstract

Background/Objectives: Wound infections represent a major category of healthcare-associated infections (HAIs) that interrupt the wound healing process, resulting in delayed wound healing and increasing the incidence of mortality, morbidity and healthcare costs. With the emergence of antibiotic resistance, there is an urgent need to find alternative therapeutic strategies capable of overcoming antibiotic resistance while simultaneously promoting wound healing. Previously, we synthesized iron oxide nanoparticles stabilized with cetyltrimethylammonium bromide (IONPs-CTAB), reported their antimicrobial activity against selected multidrug-resistant bacteria (MDR-bacteria) and SARS-CoV2 virus, and addressed their biocompatibility with the skin and eyes of rabbits. Therefore, it is hypothesized that IONPs-CTAB might be a promising alternative therapeutic agent for management of infected wounds. Methods: IONPs-CTAB were synthesized, and their successful synthesis was confirmed by FTIR, DSC-TGA, and XPS. Their antibacterial activity against three MDR-bacteria, Staphylococcus aureus (S. aureus), methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), isolated from infected wounds was investigated via the microdilution test to determine MIC/MBC, and a time–kill curve study was also performed. Subsequently, an in vivo study was conducted to assess their wound healing activity on both non-infected and infected wounds. Results: IONPs-CTAB had MIC and MBC values ranging from 125 to 250, and 500 to 1000 µg/mL, respectively. The time–kill curve study showed an effective control of bacterial growth for all tested bacteria. The vivo study demonstrated the superior wound healing activity of IONPs-CTAB compared to standard treatment on both non-infected and infected wounds. This was further confirmed by histopathological examination and biochemical analysis. Conclusions: IONPs-CTAB might be a good therapeutic alternative for the management of infected and non-infected wounds. However, future studies are still required to assess their long-term safety and the possibility of their extravasation to systemic circulation, with their potential accumulation in various organs after a long-term application.