title: 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.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China.
authors.forename: Rangrang
authors.initials: R
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China. Electronic address: aipingtong@scu.edu.cn.
authors.forename: Aiping
authors.initials: A
authors.lastname: Tong
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China.
authors.forename: Meijia
authors.initials: M
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China.
authors.forename: Liangxue
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing 100084, PR China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China. Electronic address: guogang@scu.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage* / Q000494:pharmacology; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D065546:Drug Liberation; D004355:Drug Stability; D057809:HEK293 Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013499:Surface Properties; D013696:Temperature; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D023181:Antimicrobial Cationic Peptides; D004268:DNA-Binding Proteins; D020100:Hydrogels; D019344:Lactic Acid; D020442:Poloxamer; D011091:Polyesters; D011108:Polymers; D017382:Reactive Oxygen Species; C000597433:GPR15LG protein, human; C033616:poly(lactide)
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)