细胞内
金黄色葡萄球菌
抗生素
微生物学
细胞内寄生虫
细菌
细胞毒性
化学
HEK 293细胞
药理学
生物
生物化学
体外
受体
遗传学
作者
Manasi Jambhrunkar,Sajedeh Maghrebi,Divya Doddakyathanahalli,Anthony Wignall,Clive A. Prestidge,Kristin Elizabeth Bremmell
出处
期刊:Pharmaceutics
[MDPI AG]
日期:2023-03-23
卷期号:15 (4): 1037-1037
被引量:1
标识
DOI:10.3390/pharmaceutics15041037
摘要
Intracellular bacteria are inaccessible and highly tolerant to antibiotics, hence are a major contributor to the global challenge of antibiotic resistance and recalcitrant clinical infections. This, in tandem with stagnant antibacterial discovery, highlights an unmet need for new delivery technologies to treat intracellular infections more effectively. Here, we compare the uptake, delivery, and efficacy of rifampicin (Rif)-loaded mesoporous silica nanoparticles (MSN) and organo-modified (ethylene-bridged) MSN (MON) as an antibiotic treatment against small colony variants (SCV) Staphylococcus aureus (SA) in murine macrophages (RAW 264.7). Macrophage uptake of MON was five-fold that of equivalent sized MSN and without significant cytotoxicity on human embryonic kidney cells (HEK 293T) or RAW 264.7 cells. MON also facilitated increased Rif loading with sustained release, and seven-fold increased Rif delivery to infected macrophages. The combined effects of increased uptake and intracellular delivery of Rif by MON reduced the colony forming units of intracellular SCV-SA 28 times and 65 times compared to MSN-Rif and non-encapsulated Rif, respectively (at a dose of 5 µg/mL). Conclusively, the organic framework of MON offers significant advantages and opportunities over MSN for the treatment of intracellular infections.
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