Contact lens delivery improves therapeutic efficacy of nintedanib in rabbit eyes with alkali burn.

Abstract

Nintedanib is a prescription drug for treating lung fibrosis. There is so far no report of its antifibrotic activity in the cornea. This study investigates its therapeutic efficacy as topical solution or through drug-loaded contact lenses following alkali injury in rabbit eye. Nintedanib was loaded in Vitamin E containing contact lenses and it's in vitro loading and release kinetics were evaluated. Topical drop of 0.3 % nintedanib solution was instilled on intact cornea of rabbit eye or a contact lens loaded with 0.02 % nintedanib was implanted on the cornea. Aqueous humor paracentesis was conducted at different time points for pharmacokinetics. Alkali injury was induced in one eye of rabbit, with 1 N NaOH, followed by treatment with PBS drops, nintedanib drops or nintedanib contact lens. Ocular examination included slit lamp grading for corneal fibrosis and neovascularization, OCT and histopathology. 20 % Vitamin E loaded contact lenses showed sustained drug release for a period of 12 days in vitro, however, in vivo, there was no detectable drug in the aqueous humor in any group. There was significant decrease in corneal neovascularization in eyes with contact lenses at day 14, but corneal thinning and perforations were recorded. Histopathological sections showed remarkably reduced neo vessels, inflammatory cells and fibrosis in eyes that received the contact lenses. Nintedanib delivery through contact lens establishes as a promising therapeutic option for arresting corneal neovascularization, further studies are warranted for optimising safety and ocular availability.