In situ gel-forming AP-57 peptide delivery system for cutaneous wound healing
In situ gel-forming AP-57 peptide delivery system for cutaneous wound healing
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DOI：
10.1016/j.ijpharm.2015.09.005
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发表时间：
2015-11-10
影响因子：
5.8
通讯作者：
Guo, Gang
中科院分区：
文献类型：
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作者：
Li, Xiaoling;Fan, Rangrang;Guo, Gang
原位凝胶系统作为局部给药系统在皮肤创伤中的应用引起了人们极大的兴趣。越来越多的证据表明，抗菌肽在创伤愈合过程中起着关键作用。为探索抗菌肽在伤口愈合中的潜在应用，本研究首先构建了可生物降解的聚L-乳酸-普流罗尼克L35-聚L-乳酸（PLLA-L35-PLLA）复合材料。以该聚合物为基础，制备了载人抗菌肽57（AP-57）纳米粒与温敏水凝胶组成的可注射原位凝胶形成系统，并应用于皮肤创伤愈合。AP-57肽被具有高载药量和包封效率的生物相容性纳米颗粒（AP-57-NP）包封。将AP-57-NP进一步包封在热敏性水凝胶（AP-57-NPs-H）中以促进其在皮肤伤口修复中的应用。结果，AP-57-NPs-H在延长的时间内释放AP-57，并且在体外表现出相当低的细胞毒性和高的抗氧化活性。此外，AP-57-NPs-H在室温下是自由流动的液体，并且在施加到伤口上时可以在没有任何交联剂的情况下形成不流动的凝胶。采用SD大鼠全层皮肤缺损模型进行的体内伤口愈合试验表明，AP-57-NPs-H可显著促进伤口愈合。在手术后第14天，AP-57-NPs-H治疗组显示96.78 +/-3.12%的几乎完全伤口闭合，而NS、NPs-H和AP-57-NPs组分别恢复约68.78 +/-4.93%、81.96 +/-3.26%和87.80 +/-4.62%。组织病理学检查提示AP-57-NPs-H可通过促进创面肉芽组织形成、胶原沉积和血管生成促进皮肤创面愈合。因此，AP-57-NPs-H可能在创伤愈合中具有潜在的应用价值。(C)2015 Elsevier B. V.版权所有。
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. (C) 2015 Elsevier B.V. All rights reserved.