Liquid crystal nanoparticle platform for increased efficacy of cationic antimicrobials against biofilm infections

Chelsea R Thorn; Zlatko Kopecki; Anthony Wignall; Anita Kral; Clive A Prestidge; Nicky Thomas

doi:10.1016/j.nano.2022.102536

Liquid crystal nanoparticle platform for increased efficacy of cationic antimicrobials against biofilm infections

Nanomedicine. 2022 Jun:42:102536. doi: 10.1016/j.nano.2022.102536. Epub 2022 Feb 22.

Authors

Chelsea R Thorn¹, Zlatko Kopecki², Anthony Wignall³, Anita Kral⁴, Clive A Prestidge³, Nicky Thomas⁵

Affiliations

¹ University of South Australia, Clinical and Health Science, Adelaide, SA, Australia; The Basil Hetzel Institute for Translational Health Research, Woodville, SA, Australia; ARC Centre for Excellence in Bio-Nano Science and Technology, Adelaide, SA, Australia; Biofilm Test Facility, Cancer Research Institute, University of South Australia, Adelaide, SA, Australia.
² University of South Australia, Clinical and Health Science, Adelaide, SA, Australia; Future Industries Institute, UniSA, Mawson Lakes, SA, Australia.
³ University of South Australia, Clinical and Health Science, Adelaide, SA, Australia; ARC Centre for Excellence in Bio-Nano Science and Technology, Adelaide, SA, Australia.
⁴ University of South Australia, Clinical and Health Science, Adelaide, SA, Australia; Centre for Cancer Biology, S.A. Pathology and University of South Australia.
⁵ University of South Australia, Clinical and Health Science, Adelaide, SA, Australia; The Basil Hetzel Institute for Translational Health Research, Woodville, SA, Australia; ARC Centre for Excellence in Bio-Nano Science and Technology, Adelaide, SA, Australia; Biofilm Test Facility, Cancer Research Institute, University of South Australia, Adelaide, SA, Australia. Electronic address: nicky.thomas@unisa.edu.au.

PMID: 35202839
DOI: 10.1016/j.nano.2022.102536

Abstract

Bacterial biofilm infections tolerate high concentrations of antibiotics and are insidiously challenging to treat. Liquid crystal nanoparticles (LCNPs) advance the efficacy of tobramycin in biofilm-related infections by increasing the penetration of antibiotics across the biofilm matrix. Herewith, we develop the LCNPs as a platform technology, demonstrating that the LCNPs can increase the efficacy of two antibiotic classes (i.e. aminoglycosides and colistin) in P. aeruginosa biofilm infections. In C. elegans, the LCNPs potentiated the antimicrobial effect and significantly improved the survival of the nematodes. In mice with a full-thickness excisional wound, LCNPs were non-toxic and did not impair wound repair. Compared to the unformulated antibiotic treatment, tobramycin-LCNPs reduced the chronic bacterial load by 100-fold in the wound. This was also emulated in an ex vivo P. aeruginosa porcine wound infection model. The LCNPs represent a versatile platform technology that improves the efficacy of cationic antibiotics against biofilm infections utilizing multiple administration routes.

Keywords: Aminoglycosides; Antimicrobials; Biofilm; Lipid nanoparticles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Anti-Infective Agents*
Biofilms
Caenorhabditis elegans
Cations
Liquid Crystals*
Mice
Nanoparticles*
Pseudomonas aeruginosa
Swine
Tobramycin / pharmacology

Substances

Anti-Bacterial Agents
Anti-Infective Agents
Cations
Tobramycin