基于仿生策略构建抗菌肽增强递送系统治疗皮肤创面MRSA生物膜感染的研究

MRSA生物膜是导致皮肤创面反复感染和迁延不愈的主要原因之一，目前临床治疗困难。抗菌肽是一种新型疗法，我们前期发现抗菌肽KR-12可以有效杀灭MRSA游离细菌，但对MRSA生物膜却疗效甚微。其关键原因是KR-12不能有效穿透生物膜并稳定释放。我们既往研究结果表明，针对生物膜微环境特点设计纳米体系可以提高药物递送效率。据此，我们提出“基于仿生策略构建的右旋糖酐/明胶/KR-12纳米递送系统，通过伪装成细菌营养物质，可以有效穿透并高效杀灭MRSA生物膜，继而促进创面愈合”科学假设。为验证这一假设，本项目拟首先通过课题组成熟的静电吸引和表面修饰技术，构建并优化抗菌肽增强递送系统；然后通过课题组建立的体外及体内MRSA生物膜模型，探讨其对创面MRSA生物膜感染的治疗作用及初步机制。本研究可以为拓展抗菌肽在MRSA生物膜感染创面的临床应用提供新思路和新方法，并为其它药物递送系统的构建提供有益的参考。

MRSA biofilm is one of the main causes of repeated infection and prolonged healing of cutaneous wounds. Currently, the removal of MRSA biofilm in clinical practice is difficult. Antimicrobial peptides(AMPs) are novel therapies for drug-resistant bacteria. In the previous study, we found that KR-12 peptide could effectively eliminate planktonic MRSA bacteria but showed little effect on the already formed MRSA biofilm. The key reason is that KR-12 cannot penetrate the biofilm effectively and release stably. Our previous research indicated that the nano-system designed based on the characteristics of biofilm’s microenvironment could improve the efficiency of drug delivery. On the basis of our primary works, we hypothesize that “the dextran/gelatin/KR-12 nano-delivery system constructed based on a biomimetic strategy, can effectively penetrate and eliminate MRSA biofilm by masquerading as bacterial nutrients, thereby promoting wound healing”. To validate this hypothesis, we firstly try to construct and optimize AMPs-enhancing delivery systems by electrostatic attraction and surface modification technology reported in our previous research. Secondly, using MRSA biofilm models both in vitro and in vivo, we try to investigate the therapeutic effect and preliminary mechanism of this nanomaterial in treating cutaneous wounds infected with MRSA biofilm. This study will not only provide new ideas and new strategies for the clinical application of AMPs in the therapy of wounds infected with MRSA biofilm, but also provide beneficial references for the construction of other drug delivery systems.