TY - JOUR
T1 - Monitoring local delivery of vancomycin from gelatin nanospheres in zebrafish larvae
AU - Zhang, Xiaolin
AU - Song, Jiankang
AU - Klymov, Alexey
AU - Zhang, Yang
AU - de Boer, Leonie
AU - Jansen, John A.
AU - van den Beucken, Jeroen J.J.P.
AU - Yang, Fang
AU - Zaat, Sebastian A.J.
AU - Leeuwenburgh, Sander C.G.
N1 - Funding Information:
The authors would like to thank Prof Dr Graham Lieschke from Monash University, Australia, and Prof Dr Steven Renshaw from Sheffield University, UK, for providing the zebrafish transgenic lines (mpeg1:Gal4/UAS:Kaede) and (fms:Gal4/UAS:mCherry), respectively.
Funding Information:
Xiaolin Zhang was financially supported by IBIZA project of the BioMedical Material (BMM) program, co-funded by the Dutch Ministry of Economic Affairs. Jiankang Song was financially supported by the Chinese Scholarship Council under foundation number 201206150058. The authors report no other conflicts of interest in this work.
Publisher Copyright:
© 2018 Zhang et al.
PY - 2018/9/13
Y1 - 2018/9/13
N2 - 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.
AB - 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.
KW - Biodistribution
KW - Cell-material interaction
KW - Fluorescence microscopy
KW - In vivo real-time monitoring
KW - Intracellular infection
KW - Staphylococcus aureus
UR - http://www.scopus.com/inward/record.url?scp=85055637372&partnerID=8YFLogxK
U2 - 10.2147/IJN.S168959
DO - 10.2147/IJN.S168959
M3 - Article
C2 - 30254441
AN - SCOPUS:85055637372
SN - 1176-9114
VL - 13
SP - 5377
EP - 5394
JO - International journal of nanomedicine
JF - International journal of nanomedicine
ER -