Enhanced in vivo antifungal activity of novel cell penetrating peptide natamycin conjugate for efficient fungal keratitis management

Abstract

Natamycin is the only FDA approved drug that is used as a first line of treatment for fungal keratitis caused by filamentous fungi, however natamycin is known for poor corneal penetration. Cell penetrating peptides (CPPs) are emerging nanocarriers for the enhanced delivery of various macromolecules owing to their distinct cellular translocation ability. In the present study, tissue penetration ability and antifungal efficacy of CPP (Tat2) conjugated natamycin has been investigated and compared with natamycin alone in vivo. Results show that Tat2natamycin exhibits five- fold higher ocular penetration than natamycin alone when given topically. Complete resolution of fungal keratitis in 44% of the animals in Tat2natamycin treated group as compared to only 13% of the animals in natamycin treated group further highlights its increased antifungal efficacy. Hence, this conjugate is a promising antifungal molecule with enhanced ocular penetration as well as antifungal efficacy against selected fungal species.