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

<b>Background:</b> 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 promo...

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Main Authors: Qin Qin, Wenxing Wu, Ling Che, Xing Zhou, Diedie Wu, Xiaohui Li, Yumin Yang, Jie Lou
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/1/7
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author Qin Qin
Wenxing Wu
Ling Che
Xing Zhou
Diedie Wu
Xiaohui Li
Yumin Yang
Jie Lou
author_facet Qin Qin
Wenxing Wu
Ling Che
Xing Zhou
Diedie Wu
Xiaohui Li
Yumin Yang
Jie Lou
author_sort Qin Qin
collection DOAJ
description <b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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 <i>E. coli</i> and <i>S. aureus</i>. 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. <b>Conclusions:</b> 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.
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spelling doaj-art-21b099b099f34d70bc46d153f0edf1902025-01-24T13:45:33ZengMDPI AGPharmaceutics1999-49232024-12-01171710.3390/pharmaceutics17010007Computer-Aided Construction and Evaluation of Poly-L-Lysine/Hyodeoxycholic Acid Nanoparticles for Hemorrhage and Infection TherapyQin Qin0Wenxing Wu1Ling Che2Xing Zhou3Diedie Wu4Xiaohui Li5Yumin Yang6Jie Lou7School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, ChinaDepartment of Pharmaceutics, College of Pharmacy, Army Medical University, Chongqing 400038, ChinaDepartment of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing 100853, ChinaYunnan Key Laboratory of Stem Cell and Regenerative Medicine, Science and Technology Achievement Incubation Center, Kunming Medical University, Kunming 650500, ChinaSchool of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, ChinaDepartment of Pharmaceutics, College of Pharmacy, Army Medical University, Chongqing 400038, ChinaDepartment of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing 100853, ChinaSchool of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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 <i>E. coli</i> and <i>S. aureus</i>. 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. <b>Conclusions:</b> 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.https://www.mdpi.com/1999-4923/17/1/7computer simulationhemostasisantibacterialpoly-L-lysinecholic acid derivativesdrug delivery
spellingShingle Qin Qin
Wenxing Wu
Ling Che
Xing Zhou
Diedie Wu
Xiaohui Li
Yumin Yang
Jie Lou
Computer-Aided Construction and Evaluation of Poly-L-Lysine/Hyodeoxycholic Acid Nanoparticles for Hemorrhage and Infection Therapy
Pharmaceutics
computer simulation
hemostasis
antibacterial
poly-L-lysine
cholic acid derivatives
drug delivery
title Computer-Aided Construction and Evaluation of Poly-L-Lysine/Hyodeoxycholic Acid Nanoparticles for Hemorrhage and Infection Therapy
title_full Computer-Aided Construction and Evaluation of Poly-L-Lysine/Hyodeoxycholic Acid Nanoparticles for Hemorrhage and Infection Therapy
title_fullStr Computer-Aided Construction and Evaluation of Poly-L-Lysine/Hyodeoxycholic Acid Nanoparticles for Hemorrhage and Infection Therapy
title_full_unstemmed Computer-Aided Construction and Evaluation of Poly-L-Lysine/Hyodeoxycholic Acid Nanoparticles for Hemorrhage and Infection Therapy
title_short Computer-Aided Construction and Evaluation of Poly-L-Lysine/Hyodeoxycholic Acid Nanoparticles for Hemorrhage and Infection Therapy
title_sort computer aided construction and evaluation of poly l lysine hyodeoxycholic acid nanoparticles for hemorrhage and infection therapy
topic computer simulation
hemostasis
antibacterial
poly-L-lysine
cholic acid derivatives
drug delivery
url https://www.mdpi.com/1999-4923/17/1/7
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