Antimicrobial Activity of Poly-epsilon-lysine Peptide Hydrogels Against Pseudomonas aeruginosa

Abstract

To determine the antimicrobial activity of poly-epsilon-lysine (pɛK) functionalization of hydrogels against Pseudomonas aeruginosa. METHODS. Antimicrobial activities of pɛK and pɛK+ hydrogels were tested against both keratitis and a laboratory strain of P aeruginosa at a range of inocula sizes, over 4 and 24 hours. The number of viable CFU on pɛK and pɛK+ hydrogels or commercial contact lenses (CL) was investigated. Ex vivo porcine corneas were inoculated with P aeruginosa PAO1 (10 3 CFU) and incubated with pɛK+ hydrogels or commercial hydrogel CL for 24 hours and the effects of infection determined. RESULTS. PɛK+ hydrogels showed log reductions in viable CFU compared with pɛK hydrogels for all P aeruginosa strains, depending on inocula sizes and incubation time. After 24 hours pɛK+ hydrogels showed >5 and >7.5 log reduction in CFU compared with commercial hydrogel CL at 10 3 and 10 6 CFU, respectively. In an ex vivo porcine corneal infection model, pɛK+ hydrogels led to a significant decrease in viable PAO1 CFU and histologic analysis indicated a decreased infiltration of PAO1 into the stroma. CONCLUSIONS. PɛK+ hydrogels demonstrated enhanced antimicrobial activity versus nonfunctionalized pɛK hydrogels against clinically relevant P aeruginosa strains. PɛK+ hydrogels have the potential to be used as a bandage CL with innate antimicrobial characteristics to minimize the risk of microbial keratitis.

Risk Factors, Clinical Outcomes, and Prognostic Factors of Bacterial Keratitis: The Nottingham Infectious Keratitis Study

“…To overcome this clinical barrier, a number of novel and emerging technologies, including MALDI-TOF mass spectrometry (39,40), IVCM (41), polymerase chain reaction (PCR) (42), next generation sequencing (43), and artificial intelligence-assisted platforms (44), have been developed and/or implemented in clinical practise. In addition, emerging treatment such as therapeutic corneal collagen cross-linking, ultraviolet C treatment, polymer-based treatment, and antimicrobial peptides may serve as useful adjunctive treatment in the near future, improving the management and treatment outcome of infectious keratitis (45)(46)(47)(48)(49).…”

Antimicrobial Peptide Expression at the Ocular Surface and Their Therapeutic Use in the Treatment of Microbial Keratitis

“…In vivo , Brilcidin 0.5% was equally efficacious to vancomycin in reducing methicillin-resistant S. aureus (MRSA) in rabbit eyes ( Kowalski et al, 2016 ). Given the success in studies on the exogenous application of AMPs, researchers have experimented with delivering AMPs in different vehicles, including contact lenses, hydrogels, and liposomes ( Kumar et al, 2011 ; Dutta et al, 2016 ; Gallagher et al, 2016 ; Kennedy et al, 2020 ; Kalaiselvan et al, 2021 ). In an in vivo rabbit model, melimine-coated contact lenses significantly reduced P. aeruginosa microbial keratitis, had lower ocular scores, and improved ocular signs compared to controls ( Dutta et al, 2016 ).…”

BCLA CLEAR – Contact lens technologies of the future

“…Several reports exist on the development of poly-epsilon lysine containing bandage contact lenses which can bind other antimicrobials such as penicillin G, the antimicrobial peptide Mel4 or amphotericin B and be used to treat both fungal and microbial keratitis [335][336][337][338]. Poly-epsilon lysine is a naturally occurring antimicrobial peptide that is nontoxic, is used as both an emulsifier and food preservative, and is classified as "generally regarded as safe" by many regulatory authorities.…”