Abstract
Skin is the largest mechanical barrier against invading pathogens. Following skin injury, the healing process immediately starts to regenerate the damaged tissues and to avoid complications that usually include colonization by pathogenic bacteria, leading to fever and sepsis, which further impairs and complicates the healing process. So, there is an urgent need to develop a novel pharmaceutical material that promotes the healing of infected wounds. The present work aimed to prepare and evaluate the efficacy of novel azithromycin-loaded zinc oxide nanoparticles (AZM-ZnONPs) in the treatment of infected wounds. The Box–Behnken design and response surface methodology were used to evaluate loading efficiency and release characteristics of the prepared NPs. The minimum inhibitory concentration (MIC) of the formulations was determined against Staphylococcus aureus and Escherichia coli. Moreover, the anti-bacterial and wound-healing activities of the AZM-loaded ZnONPs impregnated into hydroxyl propyl methylcellulose (HPMC) gel were evaluated in an excisional wound model in rats. The prepared ZnONPs were loaded with AZM by adsorption. The prepared ZnONPs were fully characterized by XRD, EDAX, SEM, TEM, and FT-IR analysis. Particle size distribution for the prepared ZnO and AZM-ZnONPs were determined and found to be 34 and 39 nm, respectively. The mechanism by which AZM adsorbed on the surface of ZnONPs was the best fit by the Freundlich model with a maximum load capacity of 160.4 mg/g. Anti-microbial studies showed that AZM-ZnONPs were more effective than other controls. Using an experimental infection model in rats, AZM-ZnONPs impregnated into HPMC gel enhanced bacterial clearance and epidermal regeneration, and stimulated tissue formation. In conclusion, AZM -loaded ZnONPs are a promising platform for effective and rapid healing of infected wounds.
Highlights
Wound healing is a critical process that involves four stages, including hemostasis, inflammation, proliferation, and maturation [1,2]
Considering the interesting findings of ZnONPs and AZM in the healing process of infected wounds, the major objective of our study is to explore the effect of AZM-ZnONPs for treating infected wounds
Zn–O stretching mode for wurtzite zinc oxide (ZnO) was identified in the investigated ZnO and AZM-ZnONPs in the far infrared region at wave numbers between 430 and 445 cm−1
Summary
Wound healing is a critical process that involves four stages, including hemostasis, inflammation, proliferation, and maturation [1,2]. Any interruption of these stages will retard the repair of damaged tissues. The healing process can become impaired and complicated because of infection by pathogenic bacteria that colonize the damaged tissues, with increasing incidence of spreading the infection and systemically leading to fever and sepsis [3]. There is an urgent need for the development and discovery of novel materials that cure infected wounds and accelerate the healing process. Metal and metal oxide nanoparticles [5,6,7] exhibit remarkable antibacterial activities against different pathogens, in addition to their low toxicity profile [8,9]
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