Han Huiyu, Chen Lianheng, Liang Shu, Lü Jiawei, Wu Yashi, Wang Xiongjun, Xu Fei, Ge Lanlan, Xiao Lingyun
Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou, China.
Center Lab of Longhua Branch, Department of Infectious Disease, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Southern University of Science and Technology, Shenzhen, Guangdong, China.
Front Bioeng Biotechnol. 2023 Aug 10;11:1243525. doi: 10.3389/fbioe.2023.1243525. eCollection 2023.
Burn wounds are susceptible to bacterial infections, including Methicillin-resistant (MRSA), which typically form biofilms and exhibit drug resistance. They also have specific feature of abundant exudate, necessitating frequent drug administration. Shikonin (SKN) has been reported to reverse MRSA drug resistance and possesses anti-biofilm and wound healing properties, however, it suffers from drawbacks of low solubility and instability. In this study, we developed PLA-HPG based bioadhesive nanoparticles SKN/BNP, which demonstrated a drug loading capacity of about 3.6%, and exhibited sustained-release behavior of SKN. The aldehyde groups present on the surface of BNP improved the local adhesion of SKN/BNP both and , thereby reducing the frequency of drug dosing in exudate-rich burn wounds. BNP alone enhanced proliferation and migration of the fibroblast, while SKN/BNP promoted fibroblast proliferation and migration as well as angiogenesis. Due to its bioadhesive property, BNP directly interacted with biofilm and enhanced the efficacy of SKN against MRSA biofilm . In a mouse model of MRSA-infected burn wounds, SKN/BNP demonstrated improved anti-biofilm and wound healing efficiency. Overall, our findings suggest that SKN/BNP holds great promise as a novel and effective treatment option for clinical applications in MRSA-infected burn wounds.
烧伤创面易受细菌感染,包括耐甲氧西林金黄色葡萄球菌(MRSA),这种细菌通常会形成生物膜并表现出耐药性。烧伤创面还有渗出物丰富的特点,这就需要频繁给药。已有报道称紫草素(SKN)可逆转MRSA的耐药性,具有抗生物膜和促进伤口愈合的特性,然而,它存在溶解度低和稳定性差的缺点。在本研究中,我们开发了基于聚乳酸-聚乙二醇(PLA-HPG)的生物粘附纳米颗粒SKN/BNP,其载药量约为3.6%,并表现出SKN的缓释行为。BNP表面存在的醛基提高了SKN/BNP在伤口局部的粘附力,从而减少了在渗出物丰富的烧伤创面的给药频率。单独的BNP可增强成纤维细胞的增殖和迁移,而SKN/BNP则可促进成纤维细胞的增殖、迁移以及血管生成。由于其生物粘附特性,BNP直接与生物膜相互作用,增强了SKN对MRSA生物膜的疗效。在MRSA感染的烧伤创面小鼠模型中,SKN/BNP表现出更高的抗生物膜和伤口愈合效率。总体而言,我们的研究结果表明,SKN/BNP作为一种新型有效的治疗方法,在MRSA感染的烧伤创面临床应用中具有巨大潜力。