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用于出血和感染治疗的聚-L-赖氨酸/猪去氧胆酸纳米颗粒的计算机辅助构建与评价

Computer-Aided Construction and Evaluation of Poly-L-Lysine/Hyodeoxycholic Acid Nanoparticles for Hemorrhage and Infection Therapy.

作者信息

Qin Qin, Wu Wenxing, Che Ling, Zhou Xing, Wu Diedie, Li Xiaohui, Yang Yumin, Lou Jie

机构信息

School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China.

Department of Pharmaceutics, College of Pharmacy, Army Medical University, Chongqing 400038, China.

出版信息

Pharmaceutics. 2024 Dec 24;17(1):7. doi: 10.3390/pharmaceutics17010007.

Abstract

Traumatic hemorrhage and infection are major causes of mortality in wounds caused by battlefield injuries, hospital procedures, and traffic accidents. Developing a multifunctional nano-drug capable of simultaneously controlling bleeding, preventing infection, and promoting wound healing is critical. This study aimed to design and evaluate a nanoparticle-based solution to address these challenges effectively. Using a one-pot assembly approach, we prepared a series of nanoparticles composed of poly-L-lysine and hyodeoxycholic acid (PLL-HDCA NPs). Theoretical simulations and experimental studies were combined to optimize their structure and functionality. In vitro platelet aggregation, antibacterial assays, cytotoxicity tests, and hemolysis evaluations were performed. In vivo efficacy was assessed in various hemorrhage models, a full-thickness skin defect model, and a skin irritation test. PLL-HDCA NPs demonstrated effective induction of platelet aggregation and significantly reduced bleeding time and blood loss in mouse models, including tail vein, femoral vein, artery, and liver bleeding. Antibacterial assays revealed strong activity against and . Wound healing studies showed that PLL-HDCA NPs promoted tissue repair in a full-thickness skin defect model. Cytotoxicity and hemolysis tests indicated minimal impact on human cells and significantly reduced hemolysis rates compared to PLL alone. Skin irritation tests confirmed the safety of PLL-HDCA NPs for external application. PLL-HDCA NPs represent a safe, efficient, and multifunctional nano-drug suitable for topical applications to control bleeding, combat infection, and facilitate wound healing, making them promising candidates for use in battlefield and hospital settings.

摘要

创伤性出血和感染是战场伤、医院手术及交通事故所致伤口死亡的主要原因。开发一种能够同时控制出血、预防感染并促进伤口愈合的多功能纳米药物至关重要。本研究旨在设计并评估一种基于纳米颗粒的解决方案,以有效应对这些挑战。我们采用一锅组装法制备了一系列由聚-L-赖氨酸和猪去氧胆酸组成的纳米颗粒(PLL-HDCA NPs)。将理论模拟与实验研究相结合,以优化其结构和功能。进行了体外血小板聚集、抗菌测定、细胞毒性测试和溶血评估。在各种出血模型、全层皮肤缺损模型和皮肤刺激性试验中评估了体内疗效。PLL-HDCA NPs在小鼠模型中显示出有效诱导血小板聚集的作用,并显著缩短了包括尾静脉、股静脉、动脉和肝脏出血在内的出血时间和失血量。抗菌测定显示对[具体细菌名称1]和[具体细菌名称2]有很强的活性。伤口愈合研究表明,PLL-HDCA NPs在全层皮肤缺损模型中促进了组织修复。细胞毒性和溶血测试表明,与单独的PLL相比,其对人类细胞的影响最小,溶血率显著降低。皮肤刺激性试验证实了PLL-HDCA NPs外用的安全性。PLL-HDCA NPs是一种安全、高效且多功能的纳米药物,适用于局部应用以控制出血、对抗感染并促进伤口愈合,使其有望用于战场和医院环境。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be53/11768166/a2a0cf6dbd42/pharmaceutics-17-00007-g001.jpg

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