Liquid Crystal Nanoparticles Enhance Tobramycin Efficacy in a Murine Model of Pseudomonas aeruginosa Biofilm Wound Infection
Date
2022
Authors
Thorn, C.R.
Wignall, A.
Kopecki, Z.
Kral, A.
Prestidge, C.A.
Thomas, N.
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Journal article
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ACS Infectious Diseases, 2022; 8(4):841-854
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Chronic <i>Pseudomonas aeruginosa</i> wound infections are highly prevalent and often untreatable due to biofilm formation, resulting in high antimicrobial tolerance. Standard antibiotic therapy for <i>P. aeruginosa</i> infections involves tobramycin, yet it is highly ineffective as monotherapy as tobramycin cannot penetrate the biofilm to elicit its antimicrobial effect. Lipid liquid crystal nanoparticles (LCNPs) have previously been shown to increase the antimicrobial efficacy and penetration of tobramycin against <i>P. aeruginosa</i> biofilms <i>in vitro</i> and <i>ex vivo.</i> Here, for the first time, we have developed a chronic <i>P. aeruginosa</i> biofilm infection in full-thickness wounds in mice to examine the potential of LCNPs to improve the effect of tobramycin, preclinically. After three doses, administered once a day, tobramycin-LCNPs significantly reduced the <i>P. aeruginosa</i> bacterial load in murine wounds 1000-fold more than unformulated tobramycin, which in turn showed no significant difference to the saline control treatment. Consistent with the improved <i>P. aeruginosa</i> eradication, the tobramycin-LCNPs promoted wound healing. In comparison to previous <i>in vitro</i> and <i>ex vivo</i> data, we show a strong <i>in vitro-in vivo</i> correlation between <i>P. aeruginosa</i> biofilm infection models. The enhanced activity of tobramycin-LCNPs <i>in vivo</i> in the preclinical murine model demonstrates the strong potential of LCNPs as a next-generation formulation approach to improve the efficacy of tobramycin against <i>P. aeruginosa</i> biofilm wound infections.
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Data source: Supporting information, https://pubs.acs.org/doi/10.1021/acsinfecdis.1c00606?goto=supporting-info
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Copyright 2021 American Chemical Society