Non-lamellar lyotropic liquid crystalline nanoparticles enhance the antibacterial effects of rifampicin against Staphylococcus aureus

JOURNAL OF COLLOID AND INTERFACE SCIENCE

卷:519

Article

Nhiem Tran¹  Hocquet, Marion^2,3  Eon, Blandine^2,3  Sangwan, Parveen²  Ratcliffe, Julian²  Hinton, Tracey M.²  White, Jacinta²  Ozcelik, Berkay²  Reynolds, Nicholas P.⁴  Muir, Benjamin W.² 

[1] RMIT Univ, Sch Sci, 124 La Trobe St, Melbourne, Vic 3000, Australia

[2] CSIRO Mfg, Clayton, Vic 3168, Australia

[3] Chim Paris Tech, Paris, France

[4] Swinburne Univ Technol, ARC Training Ctr Biodevices, Fac Sci Engn & Technol, Hawthorn, Vic 3122, Australia

关键词: Lipid;    Nanoparticles;    Cubosome;    Antibacterial;    Rifampicin;    MIC;    Cytotoxicity;   

DOI  :  10.1016/j.jcis.2018.02.048

来源: Elsevier

【 摘 要 】

The fight against infection in an era of emerging antibiotic resistant bacteria is one of the grandest scientific challenges facing society today. Nano-carriers show great promise in improving the antibacterial activity of antibiotics as they are able to enhance their solubility, provide sustained release and reduce toxic side effects via specifically targeting infection sites. Here, we investigate the antibacterial effect of two lipidic nano-carriers that contain the poorly soluble antibiotic rifampicin in their bilayers. One nanoparticle is assembled solely from the lipid monoolein, thus is neutral at physiological pH and the other contains a mixture of monoolein and the cationic lipid N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate (DOTAP), thus is positively charged. Our results show that rifampicin-loaded nanoparticles reduce the minimum inhibitory concentration against Staphylococcus aureus compared to rifampicin alone, however this reduction was most pronounced for the positively charged nanoparticles. Fluorescent microscopy revealed binding of all nanoparticles to the bacteria and enhanced binding was observed for the charged nanoparticles. This suggests that the cationic lipids promote electrostatic interactions with the negatively charged bacterial membrane. Forster resonance energy transfer demonstrated that the cationic charged nanoparticles were able to fuse with bacterial membranes whilst atomic force microscopy and transmission electron microscopy revealed structural damage to the bacterial membranes caused by the nanoparticles. Significantly, we identified a concentration window in which the nanoparticles exhibited antibacterial activity while not affecting HeLa and CHO cell viability. This ability to improve the efficacy of antibiotics without affecting their eukaryotic cytotoxicity is of significant importance for future development of nanomedicine based strategies to combat infections. (C) 2018 Elsevier Inc. All rights reserved.

【 授权许可】

Free