The effect of immobilisation strategies on the ability of peptoids to reduce the adhesion of P. aeruginosa strains to contact lenses

Manjulatha Sara; Sudip Chakraborty; Renxun Chen; Dennis Palms; Georgio Katsifis; Zhongyan Li; Syamak Farajikhah; Vinod Massedupally; Alex Hui; Edgar H H Wong; Naresh Kumar; Krasimir Vasilev; David Mackenzie; Linda Losurdo; Farida Dehghani; Havard Jenssen; Kristian Sorensen; Jennifer S Lin; Annelise E Barron; Mark Willcox

doi:10.1016/j.exer.2024.110149

The effect of immobilisation strategies on the ability of peptoids to reduce the adhesion of P. aeruginosa strains to contact lenses

Exp Eye Res. 2025 Jan:250:110149. doi: 10.1016/j.exer.2024.110149. Epub 2024 Nov 20.

Authors

Manjulatha Sara¹, Sudip Chakraborty², Renxun Chen³, Dennis Palms⁴, Georgio Katsifis⁵, Zhongyan Li⁶, Syamak Farajikhah⁷, Vinod Massedupally⁸, Alex Hui⁹, Edgar H H Wong¹⁰, Naresh Kumar¹¹, Krasimir Vasilev¹², David Mackenzie¹³, Linda Losurdo¹⁴, Farida Dehghani¹⁵, Havard Jenssen¹⁶, Kristian Sorensen¹⁷, Jennifer S Lin¹⁸, Annelise E Barron¹⁹, Mark Willcox²⁰

Affiliations

¹ School of Optometry and Vision Science, UNSW Sydney, Australia. Electronic address: Manjulatha.sara@unsw.edu.au.
² School of Chemistry, UNSW Sydney, Australia. Electronic address: s.chakraborty@unsw.edu.au.
³ School of Chemistry, UNSW Sydney, Australia. Electronic address: r.chen@unsw.edu.au.
⁴ Biomedical Nanoengineering Laboratory, College of Medicine and Public Health, Flinders University, Bedford Park, SA, 5042, Australia. Electronic address: dennis.palms@flinders.edu.au.
⁵ School of Physics, University of Sydney, NSW, 2006, Australia. Electronic address: gkat2146@uni.sydney.edu.au.
⁶ University of Sydney, Australia. Electronic address: zhongyan.li@sydney.edu.au.
⁷ School of Chemical Engineering, UNSW Sydney, Australia. Electronic address: syamak.farajikhah@sydney.edu.au.
⁸ School of Optometry and Vision Science, UNSW Sydney, Australia. Electronic address: vinodm@unsw.edu.au.
⁹ School of Optometry and Vision Science, UNSW Sydney, Australia; Centre for Ocular Research and Education, University of Waterloo, Canada. Electronic address: alex.hui@unsw.edu.au.
¹⁰ School of Optometry and Vision Science, UNSW Sydney, Australia; School of Chemical Engineering, UNSW Sydney, Australia. Electronic address: edgar.wong@unsw.edu.au.
¹¹ School of Chemistry, UNSW Sydney, Australia. Electronic address: n.kumar@unsw.edu.au.
¹² Biomedical Nanoengineering Laboratory, College of Medicine and Public Health, Flinders University, Bedford Park, SA, 5042, Australia. Electronic address: krasimir.vasilev@flinders.edu.au.
¹³ School of Physics, University of Sydney, NSW, 2006, Australia. Electronic address: david.mckenzie@sydney.edu.au.
¹⁴ School of Physics, University of Sydney, NSW, 2006, Australia. Electronic address: linda.losurdo@sydney.edu.au.
¹⁵ University of Sydney, Australia. Electronic address: fariba.dehghani@sydney.edu.au.
¹⁶ Department of Science and Environment, Roskilde University, 4000, Roskilde, Denmark. Electronic address: jenssen@ruc.dk.
¹⁷ Department of Bioengineering, School of Medicine & School of Engineering, Standford University, California, 94305, USA. Electronic address: ksoren@stanford.edu.
¹⁸ Department of Bioengineering, School of Medicine & School of Engineering, Standford University, California, 94305, USA. Electronic address: jlin3@stanford.edu.
¹⁹ Department of Bioengineering, School of Medicine & School of Engineering, Standford University, California, 94305, USA. Electronic address: aebarron@stanford.edu.
²⁰ School of Optometry and Vision Science, UNSW Sydney, Australia. Electronic address: m.willcox@unsw.edu.au.

PMID: 39571778
DOI: 10.1016/j.exer.2024.110149

Abstract

Aim: Previous studies have demonstrated that contact lenses coated with the antimicrobial cationic peptide Mel4, a derivative of melimine, can reduce the occurrence of keratitis. However, the antimicrobial activity of Mel4 weakened over time due to its susceptibility to proteolytic degradation. Oligo-N-substituted glycine peptoids such as TM5 and TM18 possess antimicrobial properties and are resistant to proteolytic breakdown. This study focused on exploring methods for covalently attaching these peptoids to contact lenses to enhance their durability and performance in vitro.

Methods: The peptoids TM5 and TM18 were covalently attached to etafilcon lenses via carbodiimide chemistry (EDC/NHS), oxazoline plasma, and plasma ion immersion implantation (PIII). The lenses were analysed using X-ray photoelectron spectroscopy (XPS), surface charge, and hydrophobicity. Inhibition of adhesion of multidrug-resistant Pseudomonas aeruginosa and cytotoxicity on corneal epithelial cells were evaluated. The impact of moist heat sterilization on activity was also assessed.

Results: XPS confirmed peptoid binding to lenses. Peptoid coatings slightly increased contact angles (≤23°) without affecting overall charge. Peptoids, bound via carbodiimide, inhibited P. aeruginosa adhesion by over 5 log10 CFU per lens, outperforming melimine, which required six times the concentration for a 3 log10 reduction. Peptoids attached via oxazoline or PIII reduced adhesion by > 5 log10 CFU. All covalent methods significantly reduced bacterial adhesion compared to untreated lenses (P < 0.0001). Peptoid-bound lenses were non-toxic to corneal epithelial cells. Sterilization did not affect carbodiimide-treated lenses but reduced the activity of oxazoline and PIII surfaces by 1-2 log10 CFU.

Conclusion: Peptoids TM5 and TM18 effectively reduced P. aeruginosa adhesion on lenses, with carbodiimide-bound surfaces retaining activity post-sterilization, showing promise for the development of antimicrobial contact lenses.

Keywords: Antimicrobial peptoids; Contact lens; Covalent attachment; Microbial keratitis; P. aeruginosa.

MeSH terms

Bacterial Adhesion* / drug effects
Contact Lenses, Hydrophilic* / microbiology
Epithelium, Corneal / drug effects
Eye Infections, Bacterial / microbiology
Eye Infections, Bacterial / prevention & control
Humans
Methacrylates
Peptoids* / pharmacology
Photoelectron Spectroscopy*
Pseudomonas Infections / microbiology
Pseudomonas Infections / prevention & control
Pseudomonas aeruginosa* / drug effects

Substances

Peptoids
etafilcon
Methacrylates