Injectable Chitosan-Based Thermosensitive Hydrogel/Nanoparticle-Loaded System for Local Delivery of Vancomycin in the Treatment of Osteomyelitis

Jin Tao,1 Yang Zhang,2 Ao Shen,3 Yunxu Yang,1 Lu Diao,4 Luye Wang,1 Danwei Cai,4 Ying Hu1,4 1School of Pharmaceutical Sciences, Zhejiang Pharmaceutical College, Ningbo, Zhejiang, People’s Republic of China; 2Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou...

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Autores principales:	Tao J, Zhang Y, Shen A, Yang Y, Diao L, Wang L, Cai D, Hu Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	vancomycin chitosan nanoparticles injectable hydrogel osteomyelitis Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/13de8a6abd99454d9eb553b428bf1c03
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spelling	oai:doaj.org-article:13de8a6abd99454d9eb553b428bf1c032021-12-02T09:13:38ZInjectable Chitosan-Based Thermosensitive Hydrogel/Nanoparticle-Loaded System for Local Delivery of Vancomycin in the Treatment of Osteomyelitis1178-2013https://doaj.org/article/13de8a6abd99454d9eb553b428bf1c032020-08-01T00:00:00Zhttps://www.dovepress.com/injectable-chitosan-based-thermosensitive-hydrogelnanoparticle-loaded--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jin Tao,1 Yang Zhang,2 Ao Shen,3 Yunxu Yang,1 Lu Diao,4 Luye Wang,1 Danwei Cai,4 Ying Hu1,4 1School of Pharmaceutical Sciences, Zhejiang Pharmaceutical College, Ningbo, Zhejiang, People’s Republic of China; 2Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia; 4School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Ying HuZhejiang Pharmaceutical College, No. 888, East Section, Yinxian Main Road, The Zone of Higher Education, Ningbo, Zhejiang 315100, People’s Republic of ChinaTel +86 574 8822 2707Fax +86 574 8822 3023Email pharmhawk@126.comPurpose: Osteomyelitis, particularly chronic osteomyelitis, remains a major challenge for orthopedic surgeons. The traditional treatment for osteomyelitis, which involves antibiotics and debridement, does not provide a complete solution for infection and bone repair. Antibiotics such as vancomycin (VCM) are commonly used to treat osteomyelitis in clinical settings. VCM use is limited by a lack of effective delivery methods that provide sustained, high doses to entirely fill irregular bone tissue to treat infections.Methods: We engineered a chitosan (CS)-based thermosensitive hydrogel to produce a VCM-nanoparticle (NPs)/Gel local drug delivery system. The VCM-NPs were formed with quaternary ammonium chitosan and carboxylated chitosan nanoparticles (VCM-NPs) by positive and negative charge adsorption to enhance the encapsulation efficiency and drug loading of VCM, with the aim of simultaneously preventing infection and repairing broken bones. This hydrogel was evaluated in a rabbit osteomyelitis model.Results: The VCM-NPs had high encapsulation efficiency and drug loading, with values of 60.1± 2.1% and 24.1± 0.84%, respectively. When embedded in CS-Gel, the VCM-NPs maintained their particle size and morphology, and the injectability and thermosensitivity of the hydrogel, which were evaluated by injectability test and rheological measurement, were retained. The VCM-NPs/Gel exhibited sustained release of VCM over 26 days. In vitro tests revealed that the VCM-NPs/Gel promoted osteoblast proliferation and activity against Staphylococcus aureus. In vivo, VCM-NPs/Gel (with 10 mg vancomycin per rabbit) was used to treat rabbits with osteomyelitis. The VCM-NPs/Gel showed excellent anti-infection properties and accelerating bone repair under osteomyelitis conditions.Conclusion: The reported multifunctional NPs hydrogel system for local antibiotic delivery (VCM-NPs/Gel) showed bone regeneration promotion and anti-infection properties, demonstrating significant potential as a scaffold for effective treatment of osteomyelitis.Keywords: vancomycin, chitosan, nanoparticles, injectable hydrogel, osteomyelitisTao JZhang YShen AYang YDiao LWang LCai DHu YDove Medical Pressarticlevancomycinchitosannanoparticlesinjectable hydrogelosteomyelitisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 5855-5871 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	vancomycin chitosan nanoparticles injectable hydrogel osteomyelitis Medicine (General) R5-920
spellingShingle	vancomycin chitosan nanoparticles injectable hydrogel osteomyelitis Medicine (General) R5-920 Tao J Zhang Y Shen A Yang Y Diao L Wang L Cai D Hu Y Injectable Chitosan-Based Thermosensitive Hydrogel/Nanoparticle-Loaded System for Local Delivery of Vancomycin in the Treatment of Osteomyelitis
description	Jin Tao,1 Yang Zhang,2 Ao Shen,3 Yunxu Yang,1 Lu Diao,4 Luye Wang,1 Danwei Cai,4 Ying Hu1,4 1School of Pharmaceutical Sciences, Zhejiang Pharmaceutical College, Ningbo, Zhejiang, People’s Republic of China; 2Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia; 4School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Ying HuZhejiang Pharmaceutical College, No. 888, East Section, Yinxian Main Road, The Zone of Higher Education, Ningbo, Zhejiang 315100, People’s Republic of ChinaTel +86 574 8822 2707Fax +86 574 8822 3023Email pharmhawk@126.comPurpose: Osteomyelitis, particularly chronic osteomyelitis, remains a major challenge for orthopedic surgeons. The traditional treatment for osteomyelitis, which involves antibiotics and debridement, does not provide a complete solution for infection and bone repair. Antibiotics such as vancomycin (VCM) are commonly used to treat osteomyelitis in clinical settings. VCM use is limited by a lack of effective delivery methods that provide sustained, high doses to entirely fill irregular bone tissue to treat infections.Methods: We engineered a chitosan (CS)-based thermosensitive hydrogel to produce a VCM-nanoparticle (NPs)/Gel local drug delivery system. The VCM-NPs were formed with quaternary ammonium chitosan and carboxylated chitosan nanoparticles (VCM-NPs) by positive and negative charge adsorption to enhance the encapsulation efficiency and drug loading of VCM, with the aim of simultaneously preventing infection and repairing broken bones. This hydrogel was evaluated in a rabbit osteomyelitis model.Results: The VCM-NPs had high encapsulation efficiency and drug loading, with values of 60.1± 2.1% and 24.1± 0.84%, respectively. When embedded in CS-Gel, the VCM-NPs maintained their particle size and morphology, and the injectability and thermosensitivity of the hydrogel, which were evaluated by injectability test and rheological measurement, were retained. The VCM-NPs/Gel exhibited sustained release of VCM over 26 days. In vitro tests revealed that the VCM-NPs/Gel promoted osteoblast proliferation and activity against Staphylococcus aureus. In vivo, VCM-NPs/Gel (with 10 mg vancomycin per rabbit) was used to treat rabbits with osteomyelitis. The VCM-NPs/Gel showed excellent anti-infection properties and accelerating bone repair under osteomyelitis conditions.Conclusion: The reported multifunctional NPs hydrogel system for local antibiotic delivery (VCM-NPs/Gel) showed bone regeneration promotion and anti-infection properties, demonstrating significant potential as a scaffold for effective treatment of osteomyelitis.Keywords: vancomycin, chitosan, nanoparticles, injectable hydrogel, osteomyelitis
format	article
author	Tao J Zhang Y Shen A Yang Y Diao L Wang L Cai D Hu Y
author_facet	Tao J Zhang Y Shen A Yang Y Diao L Wang L Cai D Hu Y
author_sort	Tao J
title	Injectable Chitosan-Based Thermosensitive Hydrogel/Nanoparticle-Loaded System for Local Delivery of Vancomycin in the Treatment of Osteomyelitis
title_short	Injectable Chitosan-Based Thermosensitive Hydrogel/Nanoparticle-Loaded System for Local Delivery of Vancomycin in the Treatment of Osteomyelitis
title_full	Injectable Chitosan-Based Thermosensitive Hydrogel/Nanoparticle-Loaded System for Local Delivery of Vancomycin in the Treatment of Osteomyelitis
title_fullStr	Injectable Chitosan-Based Thermosensitive Hydrogel/Nanoparticle-Loaded System for Local Delivery of Vancomycin in the Treatment of Osteomyelitis
title_full_unstemmed	Injectable Chitosan-Based Thermosensitive Hydrogel/Nanoparticle-Loaded System for Local Delivery of Vancomycin in the Treatment of Osteomyelitis
title_sort	injectable chitosan-based thermosensitive hydrogel/nanoparticle-loaded system for local delivery of vancomycin in the treatment of osteomyelitis
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/13de8a6abd99454d9eb553b428bf1c03
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Injectable Chitosan-Based Thermosensitive Hydrogel/Nanoparticle-Loaded System for Local Delivery of Vancomycin in the Treatment of Osteomyelitis

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