Abstract
Purpose :
Fungal keratitis is one of the major causes of corneal blindness worldwide. Fusarium spp is the major aetiological agent in Asia. Treatment outcome for fungal keratitis is complicated by the deeper penetration of pathogen into the corneal tissues and poor penetration of antifungal agents. We hypothesize that membrane selective cationic peptides and polymers that target the cytoplasmic membrane of fungal pathogen are excellent candidates for treating severe forms of FK. The overall objectives of this work are to determine the antifungal effectiveness of branched cationic peptides and polymers in vitro and in vivo.
Methods :
Antifungal activity of branched peptides and polymers with three different backbone were determined against a 4 different Fusarium solani strains, in accordance with the Clinical and Laboratory Standard Institute guidelines. Fungal hyphal inhibition and cytotoxicity of peptides and polymers were determined by MTS assay. For one of the polymers, the antifungal activity was determined against in a rabbit model of fungal keratitis.
Results :
All the cationic branched peptides displayed better antifungal activity (in terms of minimum inhibitory concentration) than natamycin, the only US FDA approved antifungal drug for Fungal keratitis. The fungal hyphal inhibition of the peptides and the polymers are superior to natamycin. The selectivity of peptides and polymers were comparable to that of natamycin. One of the polymers displayed excellent ocular tolerance in a rabbit model of corneal wound healing. Elevated concentrations of the polymers did not alter the wound healing rate and did not alter the protein composition of aqueous humor when compared to vehicle alone. The polymer further displayed comparable antifungal activity as natamycin in rabbit models of Fusarium keratitis, highlighting its potential to be developed as an ophthalmic antifungal. The broad spectrum antimicrobial properties and its excellent ocular tolerability are added advantages.
Conclusions :
Our results suggest that the developed peptides displayed appreciable activity against the F. solani strains as comparator antifungal. The in vivo safety and effectiveness of one of the polymers coupled with its broad spectrum antibacterial activity against drug-resistant bacteria suggest its potential as a new class of antimicrobial for treating corneal infections.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.