Monitoring local delivery of vancomycin from gelatin nanospheres in zebrafish larvae

Xiaolin Zhang,1,2,* Jiankang Song,3,* Alexey Klymov,3,* Yang Zhang,3 Leonie de Boer,1 John A Jansen,3 Jeroen JJP van den Beucken,3 Fang Yang,3 Sebastian AJ Zaat,1,* Sander CG Leeuwenburgh3,* 1Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Academic Medical Center, Un...

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Autores principales:	Zhang X, Song J, Klymov A, Zhang Y, de Boer L, Jansen JA, van den Beucken JJJP, Yang F, Zaat SAJ, Leeuwenburgh SCG
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	in vivo real-time monitoring fluorescence microscopy bio-distribution cell-material interaction Staphylococcus aureus intracellular infection Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/60328dd454404619b33a105dc0bed257
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spelling	oai:doaj.org-article:60328dd454404619b33a105dc0bed2572021-12-02T03:14:17ZMonitoring local delivery of vancomycin from gelatin nanospheres in zebrafish larvae1178-2013https://doaj.org/article/60328dd454404619b33a105dc0bed2572018-09-01T00:00:00Zhttps://www.dovepress.com/monitoring-local-delivery-of-vancomycin-from-gelatin-nanospheres-in-ze-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiaolin Zhang,1,2,* Jiankang Song,3,* Alexey Klymov,3,* Yang Zhang,3 Leonie de Boer,1 John A Jansen,3 Jeroen JJP van den Beucken,3 Fang Yang,3 Sebastian AJ Zaat,1,* Sander CG Leeuwenburgh3,* 1Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 2Department of Biomaterials Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands; 3Department of Biomaterials, Radboud University Medical Centre, Nijmegen, the Netherlands *These authors contributed equally to this work Background: Infections such as biomaterial-associated infection and osteomyelitis are often associated with intracellular survival of bacteria (eg, Staphylococcus aureus). Treatment of these infections remains a major challenge due to the low intracellular efficacy of many antibiotics. Therefore, local delivery systems are urgently required to improve the therapeutic efficacy of antibiotics by enabling their intracellular delivery. Purpose: To assess the potential of gelatin nanospheres as carriers for local delivery of vancomycin into macrophages of zebrafish larvae in vivo and into THP-1-derived macrophages in vitro using fluorescence microscopy. Materials and methods: Fluorescently labeled gelatin nanospheres were prepared and injected into transgenic zebrafish larvae with fluorescent macrophages. Both the biodistribution of gelatin nanospheres in zebrafish larvae and the co-localization of vancomycin-loaded gelatin nanospheres with zebrafish macrophages in vivo and uptake by THP-1-derived macrophages in vitro were studied. In addition, the effect of treatment with vancomycin-loaded gelatin nanospheres on survival of S. aureus-infected zebrafish larvae was investigated. Results: Internalization of vancomycin-loaded gelatin nanospheres by macrophages was observed qualitatively both in vivo and in vitro. Systemically delivered vancomycin, on the other hand, was hardly internalized by macrophages without the use of gelatin nanospheres. Treatment with a single dose of vancomycin-loaded gelatin nanospheres delayed the mortality of S. aureus-infected zebrafish larvae, indicating the improved therapeutic efficacy of vancomycin against (intracellular) S. aureus infection in vivo. Conclusion: The present study demonstrates that gelatin nanospheres can be used to facilitate local and intracellular delivery of vancomycin. Keywords: in vivo real-time monitoring, fluorescence microscopy, biodistribution, cell-material interaction, Staphylococcus aureus, intracellular infectionZhang XSong JKlymov AZhang Yde Boer LJansen JAvan den Beucken JJJPYang FZaat SAJLeeuwenburgh SCGDove Medical Pressarticlein vivo real-time monitoringfluorescence microscopybio-distributioncell-material interactionStaphylococcus aureusintracellular infectionMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 5377-5394 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	in vivo real-time monitoring fluorescence microscopy bio-distribution cell-material interaction Staphylococcus aureus intracellular infection Medicine (General) R5-920
spellingShingle	in vivo real-time monitoring fluorescence microscopy bio-distribution cell-material interaction Staphylococcus aureus intracellular infection Medicine (General) R5-920 Zhang X Song J Klymov A Zhang Y de Boer L Jansen JA van den Beucken JJJP Yang F Zaat SAJ Leeuwenburgh SCG Monitoring local delivery of vancomycin from gelatin nanospheres in zebrafish larvae
description	Xiaolin Zhang,1,2,* Jiankang Song,3,* Alexey Klymov,3,* Yang Zhang,3 Leonie de Boer,1 John A Jansen,3 Jeroen JJP van den Beucken,3 Fang Yang,3 Sebastian AJ Zaat,1,* Sander CG Leeuwenburgh3,* 1Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 2Department of Biomaterials Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands; 3Department of Biomaterials, Radboud University Medical Centre, Nijmegen, the Netherlands *These authors contributed equally to this work Background: Infections such as biomaterial-associated infection and osteomyelitis are often associated with intracellular survival of bacteria (eg, Staphylococcus aureus). Treatment of these infections remains a major challenge due to the low intracellular efficacy of many antibiotics. Therefore, local delivery systems are urgently required to improve the therapeutic efficacy of antibiotics by enabling their intracellular delivery. Purpose: To assess the potential of gelatin nanospheres as carriers for local delivery of vancomycin into macrophages of zebrafish larvae in vivo and into THP-1-derived macrophages in vitro using fluorescence microscopy. Materials and methods: Fluorescently labeled gelatin nanospheres were prepared and injected into transgenic zebrafish larvae with fluorescent macrophages. Both the biodistribution of gelatin nanospheres in zebrafish larvae and the co-localization of vancomycin-loaded gelatin nanospheres with zebrafish macrophages in vivo and uptake by THP-1-derived macrophages in vitro were studied. In addition, the effect of treatment with vancomycin-loaded gelatin nanospheres on survival of S. aureus-infected zebrafish larvae was investigated. Results: Internalization of vancomycin-loaded gelatin nanospheres by macrophages was observed qualitatively both in vivo and in vitro. Systemically delivered vancomycin, on the other hand, was hardly internalized by macrophages without the use of gelatin nanospheres. Treatment with a single dose of vancomycin-loaded gelatin nanospheres delayed the mortality of S. aureus-infected zebrafish larvae, indicating the improved therapeutic efficacy of vancomycin against (intracellular) S. aureus infection in vivo. Conclusion: The present study demonstrates that gelatin nanospheres can be used to facilitate local and intracellular delivery of vancomycin. Keywords: in vivo real-time monitoring, fluorescence microscopy, biodistribution, cell-material interaction, Staphylococcus aureus, intracellular infection
format	article
author	Zhang X Song J Klymov A Zhang Y de Boer L Jansen JA van den Beucken JJJP Yang F Zaat SAJ Leeuwenburgh SCG
author_facet	Zhang X Song J Klymov A Zhang Y de Boer L Jansen JA van den Beucken JJJP Yang F Zaat SAJ Leeuwenburgh SCG
author_sort	Zhang X
title	Monitoring local delivery of vancomycin from gelatin nanospheres in zebrafish larvae
title_short	Monitoring local delivery of vancomycin from gelatin nanospheres in zebrafish larvae
title_full	Monitoring local delivery of vancomycin from gelatin nanospheres in zebrafish larvae
title_fullStr	Monitoring local delivery of vancomycin from gelatin nanospheres in zebrafish larvae
title_full_unstemmed	Monitoring local delivery of vancomycin from gelatin nanospheres in zebrafish larvae
title_sort	monitoring local delivery of vancomycin from gelatin nanospheres in zebrafish larvae
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/60328dd454404619b33a105dc0bed257
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Monitoring local delivery of vancomycin from gelatin nanospheres in zebrafish larvae

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