In situ gel-forming AP-57 peptide delivery system for cutaneous wound healing

Abstract

In situ gel-forming system as local drug delivery system in dermal traumas has generated a great interest. Accumulating evidence shows that antimicrobial peptides play pivotal roles in the process of wound healing. Here in this study, to explore the potential application of antimicrobial peptide in wound healing, biodegradable poly(L-lactic acid)-Pluronic L35-poly(L-lactic acid) (PLLA-L35-PLLA) was developed at first. Then based on this polymer, an injectable in situ gel-forming system composed of human antimicrobial peptides 57 (AP-57) loaded nanoparticles and thermosensitive hydrogel was prepared and applied for cutaneous wound healing. AP-57 peptides were enclosed with biocompatible nanoparticles (AP-57-NPs) with high drug loading and encapsulation efficiency. AP-57-NPs were further encapsulated in a thermosensitive hydrogel (AP-57-NPs-H) to facilitate its application in cutaneous wound repair. As a result, AP-57-NPs-H released AP-57 in an extended period and exhibited quite low cytotoxicity and high anti-oxidant activity in vitro. Moreover, AP-57-NPs-H was free-flowing liquid at room temperature, and can form non-flowing gel without any crosslink agent upon applied on the wounds. In vivo wound healing assay using full-thickness dermal defect model of SD rats indicated that AP-57-NPs-H could significantly promote wound healing. At day 14 after operation, AP-57-NPs-H treated group showed nearly complete wound closure of 96.78 ± 3.12%, whereas NS, NPs-H and AP-57-NPs group recovered by about 68.78 ± 4.93%, 81.96 ± 3.26% and 87.80 ± 4.62%, respectively. Histopathological examination suggested that AP-57-NPs-H could promote cutaneous wound healing through enhancing granulation tissue formation, increasing collagen deposition and promoting angiogenesis in the wound tissue. Therefore, AP-57-NPs-H might have potential application in wound healing.

Keywords: Acetonitrile (PubChem CID: 6342); Antimicrobial peptides; Dichloromethane (PubChem CID: 6344); Dimethyl sulfoxide (PubChem CID: 679); Hematoxylin (PubChem CID: 442514); Hydrogel; Ketamine hydrochloride (PubChem CID: 15851); Nanoparticle; Paraformaldehyde (PubChem CID: 71309502); Phenol (PubChem CID: 996); Stannous octoate (PubChem CID: 9318); Wound healing; l-lactic acid (PubChem CID: 107689); trifluoroacetic (PubChem CID: 6422).