Thermosensitive-based synergistic antibacterial effects of novel LL37@ZPF-2 loaded poloxamer hydrogel for infected skin wound healing

Int J Pharm. 2025 Jan 10:125210. doi: 10.1016/j.ijpharm.2025.125210. Online ahead of print.

Abstract

Trauma healing is the process of healing after the body has been subjected to an external force and the skin and other tissues have become dissected or defective, showing the synergistic effect of various processes. Therefore, the investigation of innovative wound dressings has significant research and clinical implications. In this study, we constructed a zinc based metal-organic framework (MOF) and loaded with antimicrobial peptide LL37 to prepare LL37@ZPF-2 (ZPF = zeolite pyrimidine backbone), which was subsequently integrated with Poloxamer 407 to fabricate LL37@ZPF-2 thermosensitive hydrogel. Our study showed that in-situ packaging method can achieve encapsulation rate of 98 % and 15 % of drug loading for LL37. LL37@ZPF-2 demonstrated a higher inhibitory potency against S.aureus compared to E.coli. The Poloxamer 407-gel exhibits thermo-responsive sol-to-gel phase transition behaviors with a phase transition temperature (Tsol/gel) of ∼ 28.01℃, making it an appropriate material for wound healing. The composite hydrogel has excellent biocompatibility and hemocompatibility. A full-thickness skin defect model was built to confirm that LL37@ZPF-2 thermosensitive hydrogel dressing could inhibit bacterial growth, reduce the risk of wound infection, and stimulate angiogenesis and collagen deposition, resulting in a wound healing rate of 94.4 % on day 7 and complete healing on day 10. Our findings demonstrate that the novel thermosensitive LL37@ZPF-2 hydrogel confers good antibacterial activity, promoting cell migration and infected-wound healing properties, providing a promising platform for wound healing.

Keywords: Adhesion; Antibacterial; MOFs; Thermosensitive gel; Wound healing.