Monitoring local delivery of vancomycin from gelatin nanospheres in zebrafish larvae

• Published in: International journal of nanomedicine Vol. 13; pp. 5377 - 5394
• Main Authors: Zhang, Xiaolin, Song, Jiankang, Klymov, Alexey, Zhang, Yang, de Boer, Leonie, Jansen, John, van den Beucken, Jeroen, Yang, Fang, Zaat, Sebastian, Leeuwenburgh, Sander
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2018; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Additives; Animal genetic engineering; Animals; Antibacterial agents; Antibiotics; Antimicrobial agents; Bacteria; Bacterial infections; bio-distribution; Biological products; Biomedical materials; Care and treatment; cell-material interaction; Drug Delivery Systems; Embryos; Endocytosis - drug effects; Express delivery services; Fluorescence; Fluorescence microscopy; Fluorescent Dyes - metabolism; Gelatin - chemistry; Genetic engineering; Green Fluorescent Proteins - metabolism; Health aspects; Humans; Immune system; in vivo real-time monitoring; Infection; Injections, Intramuscular; Injections, Intravenous; intracellular infection; Larva - cytology; Larva - drug effects; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Medical research; Microscopy; Nanoparticles; Nanospheres - chemistry; Nanospheres - ultrastructure; Original Research; Osteomyelitis; Pathogens; Polymers; Staphylococcal infections; Staphylococcal Infections - drug therapy; Staphylococcal Infections - microbiology; Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus aureus infections; Staphylococcus infections; Survival Analysis; Tissue Distribution; Vancomycin; Vancomycin - administration & dosage; Vancomycin - pharmacology; Zebrafish; Zebrafish - metabolism; Zebrafish - microbiology; Netherlands; biodistribution; in vivo real-time monitoring; intracellular infection; cell-material interaction; fluorescence microscopy; Staphylococcus aureus
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S168959

Infections such as biomaterial-associated infection and osteomyelitis are often associated with intracellular survival of bacteria (eg, ). 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. 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. 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 -infected zebrafish larvae was investigated. 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 -infected zebrafish larvae, indicating the improved therapeutic efficacy of vancomycin against (intracellular) infection in vivo. The present study demonstrates that gelatin nanospheres can be used to facilitate local and intracellular delivery of vancomycin.