Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Department of Biomaterials Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands.
Int J Nanomedicine. 2018 Sep 13;13:5377-5394. doi: 10.2147/IJN.S168959. eCollection 2018.
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.
生物材料相关感染和骨髓炎等感染通常与细菌的细胞内存活有关（例如，）。由于许多抗生素对细胞内的疗效较低，因此治疗这些感染仍然是一个主要挑战。因此，迫切需要局部递送系统通过使抗生素能够递送到细胞内来提高抗生素的治疗效果。
使用荧光显微镜评估明胶纳米球作为载体将万古霉素递送至斑马鱼幼虫体内的巨噬细胞和体外 THP-1 衍生的巨噬细胞中的潜力。
制备荧光标记的明胶纳米球并注射到具有荧光巨噬细胞的转基因斑马鱼幼虫中。研究了明胶纳米球在斑马鱼幼虫中的生物分布以及载有万古霉素的明胶纳米球在体内与斑马鱼巨噬细胞的共定位和被 THP-1 衍生的巨噬细胞摄取的情况。此外，还研究了用载有万古霉素的明胶纳米球治疗对感染的斑马鱼幼虫存活率的影响。
在体内和体外均观察到巨噬细胞对载有万古霉素的明胶纳米球的内化。另一方面，没有使用明胶纳米球，系统给予的万古霉素几乎不会被巨噬细胞内化。单次给予载有万古霉素的明胶纳米球治疗可延迟感染的斑马鱼幼虫的死亡率，表明载有万古霉素的明胶纳米球在体内提高了万古霉素对（细胞内）感染的治疗效果。
本研究表明，明胶纳米球可用于促进万古霉素的局部和细胞内递送。
