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Treatment of Staphylococcus aureus skin infection in vivo using rifampicin loaded lipid nanoparticles

journal contribution
posted on 12.01.2021, 05:30 by A Walduck, P Sangwan, QA Vo, Julian Ratcliffe, J White, Benjamin Muir, N Tran
© The Royal Society of Chemistry 2020. We have previously reported on a novel nanoparticle formulation that was effective at killingStaphylococcus aureus in vitro. Here, we report for the first time, the antibacterial effects of a lipidic nano-carrier containing rifampicin (NanoRIF) which can be used to successfully treat Methicillin-ResistantS. aureus(MRSA) infection at a reduced antibiotic dosage compared to the free drug in a skin wound model in mice. The formulation used contains the lipid monoolein, a cationic lipidN-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate (DOTAP) and the antibiotic. We have shown that rifampicin-loaded nanoparticles are more effective at treating infection in the skin wound model than the antibiotic alone. Cryo-TEM was used to capture for the first time, interactions of the formed nanoparticles with the cell wall of an individual bacterium. Our data strongly indicate enhanced binding of these charged nanoparticles with the negatively charged bacterial membrane. The efficacy we have now observedin vivois of significant importance for the continued development of nanomedicine-based strategies to combat antibiotic resistant bacterial skin infections.

Funding

B. M. gratefully acknowledges funding through his CSIRO Office of the Chief Executive (OCE) Julius Career Award to conduct this research. N. T. is supported by a RMIT VC Research Fellowship. AW is supported by start-up funds from RMIT. The authors thank Mr Wil Gardner for assistance with rendering the cubic phase schematic image in Blender 2.81a.

History

Publication Date

11/09/2020

Journal

RSC Advances: an international journal to further the chemical sciences

Volume

10

Issue

55

Pagination

12p. (p. 33608-33619)

Publisher

RSC

ISSN

2046-2069

Rights Statement

The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.