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载吡非尼酮的层状液晶喷雾敷贴治疗深Ⅱ度烧伤:促进愈合和预防瘢痕。

A pirfenidone loaded spray dressing based on lyotropic liquid crystals for deep partial thickness burn treatment: healing promotion and scar prophylaxis.

机构信息

School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, P. R. China.

School of Pharmacy, Jinan University, Guangzhou 510632, P. R. China.

出版信息

J Mater Chem B. 2020 Apr 1;8(13):2573-2588. doi: 10.1039/c9tb02929j.

DOI:10.1039/c9tb02929j
PMID:32147675
Abstract

A deep partial thickness (DPT) burn injury refers to burn damage involving the epidermis and major dermis, whose prognosis depends greatly on wound management. Lack of effective management can lead to an elongated healing process and aggravated scar formation, which can severely disturb patients, both physically and mentally. A dressing with good water absorption and moderate mechanical properties is crucial for healing promotion, and the prevention of scar formation is highly desirable. In this project, a hyaluronic acid combined lyotropic liquid crystal based spray dressing (HLCSD) loaded with the anti-fibrotic drug pirfenidone (PFD) has been designed. HLCSD is expected to achieve the goals of both wound healing promotion and scar prophylaxis. Its water absorption capacity, mechanical properties, drug release behavior and phase transition are fully evaluated. HLCSD possesses low viscosity for spray administration and high levels of water absorption for exudate absorption. An in situ gel composed of self-assembled lattice nanostructures provides excellent mechanical protection to promote the healing process and steady PFD release to exert a scar prophylaxis effect. The benefit of HLCSD on the wound healing rate is verified in vivo. In the DPT burn wound model we established, HLCSD also exhibits excellent healing promotion effects, and PFD-loaded HLCSD shows scar prophylaxis effects and displays an ideal prognosis, with skin as smooth as healthy skin. The healing promotion of HLCSD is considered to be related to the alleviation of inflammation, with an obviously shortened inflammation phase, with contributions from water management, mechanical protection and anti-inflammation by HLCSD. The scar prophylaxis of PFD-loaded HLCSD is proven to be related to the regulation of collagen synthesis and degradation, involving key cytokines like TGF-β and MMP-1. Taken together, the PFD-loaded HLCSD with healing promotion and scar prophylaxis offers significant promise as a spray dressing for DPT burn injuries.

摘要

深Ⅱ度烧伤是指累及表皮和真皮大部分的烧伤损伤,其预后很大程度上取决于创面处理。如果处理不当,会导致愈合时间延长和疤痕加重,严重影响患者的身心健康。对于促进愈合和预防疤痕形成,敷料应具有良好的吸水性和适中的机械性能。本项目设计了一种载有抗纤维化药物吡非尼酮的透明质酸层状液晶喷雾敷料(HLCSD)。HLCSD 有望实现促进伤口愈合和预防疤痕形成的双重目标。我们对其吸水性、机械性能、药物释放行为和相转变等进行了全面评估。HLCSD 喷雾给药时黏度低,吸收渗出液时吸水性高。由自组装晶格纳米结构组成的原位凝胶为创面提供了优异的机械保护,促进愈合过程,并能持续释放 PFD,发挥预防疤痕形成的作用。HLCSD 促进伤口愈合的作用在体内得到了验证。在我们建立的深Ⅱ度烧伤模型中,HLCSD 也表现出良好的促进愈合作用,载 PFD 的 HLCSD 具有预防疤痕形成的作用,使皮肤恢复光滑,达到理想的预后。HLCSD 的促愈合作用被认为与减轻炎症有关,HLCSD 通过水管理、机械保护和抗炎作用,明显缩短了炎症期。载 PFD 的 HLCSD 的预防疤痕形成作用与胶原合成和降解的调节有关,涉及 TGF-β和 MMP-1 等关键细胞因子。综上所述,载 PFD 的 HLCSD 具有促进愈合和预防疤痕形成的作用,有望成为治疗深Ⅱ度烧伤的喷雾敷料。

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