An Engineered Contact Lens for Passive and Sustained Release of Lifitegrast, an Anti-Dry Eye Syndrome Drug

Abstract

Lifitegrast is an FDA-approved drug that inhibits T-cell mediated inflammation associated with dry eye syndrome (DES). Lifitegrast is a potent inhibitor of the interaction between LFA-1 on T-cells and ICAM-1 on endothelial cells at the ocular surface. While effective in treating DES, 5% (81.2 mM) lifitegrast has low drug utilization and elicits off-target effects. Here we engineer contact lenses to release therapeutically relevant doses of lifitegrast to every tear film for up to 10-hours. Lifitegrast is coupled to the polymer of the soft hydrogel lens via a photolabile (caged) crosslinker. Exposures of the lens to the 400-430 nm wavelengths of indoor daylight excite the caged crosslinker molecules and trigger a bond-cleavage reaction that releases authentic lifitegrast passively to the tear film. The photoproduct of the reaction remains chemically linked to the polymer of the single-use lens. Our studies show that passive exposures of the lens to indoor light would generate an average of 990 nM lifitegrast to every tear film in a zero-order reaction for up to 10-hours. This concentration exceeds the Kd for the interaction between ICAM-1 and LFA-1 by ~330-fold and would sustain inhibition of inflammatory responses at the ocular surface. The amount of lifitegrast released from the lens increases during exposures to outdoor sunlight. Over a 10-hour exposure to indoor light, a single lens would release 0.44% of the lifitegrast present in two drops of commercial 5% lifitegrast. Compared to tear-drop approaches, our engineered lenses would sustain the passive delivery of therapeutically relevant doses of lifitegrast over a longer period, and exhibit improved drug utilization at a lower cost. Our technology could easily be integrated into daily-use contact lenses in order to prevent inflammation at the ocular surface, dry-eye and contact lens-mediated discomfort.

Lab‐on‐a‐Contact Lens: Recent Advances and Future Opportunities in Diagnostics and Therapeutics

“…Both drugs can be released when exposed to daylight with a wavelength of 400-430 nm, which triggers a bond cleavage reaction, passively releasing timolol and lifitegrast into the surrounding body fluids. [234,244] Consequently, the future opportunities and challenges to develop photo-responsive therapeutic SCLs may arise from multifunctional integrated manufacturing, starting from the designs of materials and more drug screening with the photo-liable properties for ocular disease treatment.…”

“…Apart from the therapeutic applications of the SCLs, they are highly effective in protecting the retina from harmful UV-A1 wavelengths. [238] Molecular imprinting technology has received great attention as a contribution to advances in drug delivery in therapeutic SCLs. [288][289][290] Works with sustained HA release ability (>24 h) have been reported based on the molecular imprinting technology.…”

“…Adapted with permission. [238] Copyright 2021, Marriott et al b) The illustration of the SCL for real-time diabetic diagnosis and therapy with electrically-controlled drug release design. Adapted with permission.…”

“…Mu et al achieved controlled and sustained drug release upon exposure to indoor/outdoor daylights by binding Lifitegrast throughout the hydrogel polymer of CL via a photolabile crosslinker. Apart from the therapeutic applications of the SCLs, they are highly effective in protecting the retina from harmful UV-A1 wavelengths [244]. Molecular imprinting technology has received great attention as a contribution to advances in drug delivery in therapeutic SCLs [294][295][296].…”

“…The photoreleased lifitegrast molecules demonstrate a progressive diffusion-based manner from the lens hydrogel to reach the tear film and the conjunctiva stroma. Adapted with permission [238]. Copyright 2021, Marriott et al b) The illustration of the SCL for real-time diabetic diagnosis and therapy with electrically-controlled drug release design.…”