Accelerative effect of nanohydrogels based on chitosan/ZnO incorporated with citral to heal the infected full-thickness wounds; an experimental study.

Antimicrobial-resistant is a major challenge in to treat infected wounds, and new formulations should be produced. Citral (Citl), chitosan (Chsn), and zinc oxide (ZnO) nanoparticles may accelerate the wound healing process in terms of their antibacterial properties. This new study aimed to investigate the effects of ointments produced from ZnO/Chsn/Citl nanoparticles (NPs) to treat the infected wounds. Following the preparation of ZnO/Chsn/Citl-NPs, swelling behavior, the release of citral, toxicity, and antibacterial properties were evaluated. Base ointment, mupirocin, and ointments made from Chsn-NPs, Chsn/Citl-NPs, and ZnO/Chsn/Citl-NPs were used to treat the mice. The ointments' effects on wound contraction, total bacterial count, and immunofluorescence staining for TNF-α, TGF-β, and bFGF were tested. The synthesis of ZnO/Chsn/Citl-NPs was validated by XRD, FT-IR, DLS, and TEM findings. In higher dilutions, chitosan/citral and ZnO/Chsn/Citl-NPs indicated better antibacterial activity. Nanoparticles were safe up to concentration of the 0.5 mg/mL. The mice in Chsn/Citl and ZnO/Chsn/Citl-NPs treated groups showed higher (P < 0.05) wound contraction ratio and expressions for bFGF, and lower total bacterial count and expressions for TGF-β and TNF-α compared to control mice. Ointments prepared from ZnO/Chsn/Citl-NPs could compete with the commercial ointment of mupirocin and can be used to treat infected wounds after clinical studies.