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Exosome-encapsulated antibiotic against intracellular infections of methicillin-resistant Staphylococcus aureus

Authors Yang X, Shi G, Guo J, Wang C, He Y

Received 6 July 2018

Accepted for publication 1 October 2018

Published 29 November 2018 Volume 2018:13 Pages 8095—8104

DOI https://doi.org/10.2147/IJN.S179380

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Mohankandhasamy Ramasamy

Peer reviewer comments 2

Editor who approved publication: Dr Lei Yang


Xiaohong Yang, Gongming Shi, Jian Guo, Chenhui Wang, Yun He

Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, People’s Republic of China

Background: Staphylococcus aureus survival inside phagocytes is considered to provide a reservoir of bacteria that are relatively protected from antibiotics, thus enabling long-term colonization of the host and explaining clinical failures and relapses after antibiotic therapy.
Purpose: The objective of this study was to develop a nanovesicle using exosomes loaded with linezolid to overcome intracellular infections by pathogenic bacteria.
Methods:
Exosomes were collected from the culture supernatants of RAW 264.7 cells. Their size distribution and zeta potential were characterized by dynamic light scattering, their morphology was characterized by transmission electron microscopy, and their protein content (CD63 and Flotillin 1) was assessed by Western blotting. Linezolid was incorporated into exosomes by co-incubation at 37°C and it’s accumulation in RAW264.7 cells and release in vitro were determined by high performance liquid chromatography. The intracellular bactericidal effect was evaluated in methicillin-resistant S. aureus (MRSA)-infected macrophages in vitro and MRSA peritonitis model in vivo.
Results: We prepared a nanoformulation of the antibiotic linezolid using exosomes harvested from mouse RAW264.7 macrophages. The exosomal formulation of linezolid was more effective against intracellular MRSA infections in vitro and in vivo than the free linezolid. Our data also showed no signs of cytotoxicity in macrophages.
Conclusion: Exosomes provide an effective alternative for intracellular antibiotic delivery of antibiotic that is efficacious, cost-effective, and safe. This regimen can be viewed as a potential antimicrobial agent for use against intracellular infections.

Keywords:
exosomes, antibiotic, delivery, intracellular infection, MRSA

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