Contact Lenses Loaded with Melatonin Analogs: A Promising Therapeutic Tool against Dry Eye Disease

Abstract

Melatonin analogs topically administered evoke a potent tear secretagogue effect in rabbits. This route of drug administration requires high drug concentration and frequent dosing due to its reduced ocular surface retention. Therefore, contact lenses (CLs) have emerged as an alternative drug-delivery system that prolongs drug retention in the cornea, improving its therapeutic performance. This study explores the in vitro ability of five commercially available hydrogel CLs to act as a delivery system for melatonin analogs and the in vivo secretagogue effect of melatonin analog-loaded CLs. We soaked CLs with melatonin or melatonin analog solutions (1 mM) for 12 h. Spectroscopic assays showed that IIK7-loaded CLs led to the inadequate delivery of this compound. Conventional hydrogel lenses loaded with agomelatine released more agomelatine than silicone ones (16–33% more). In contrast, the CLs of silicone materials are more effective as a delivery system of 5-MCA-NAT than CLs of conventional materials (24–29%). The adaptation of CLs loaded with agomelatine or 5-MCA-NAT in rabbits triggered a higher tear secretion than the corresponding eye drops (78% and 59% more, respectively). These data suggest that CLs preloaded with melatonin analogs could be an adequate strategy to combat aqueous tear deficient dry eye disease.

Smart molecules in ophthalmology: Hydrogels as responsive systems for ophthalmic applications

“…To further confirm this, Navarro‐Gil et al. explored the potential of contact lenses loaded with melatonin analogs in treating DED [86] . Evaluation on rabbits showed a greater tear secretion with the agomelatine/5‐MCA‐NAT‐loaded contact lenses as compared to conventional Diquafosol tetrasodium eye drops.…”

The Therapeutic Trip of Melatonin Eye Drops: From the Ocular Surface to the Retina

“…Navarro-Gil et al explored commercially available hydrogel CLs as a delivery system for melatonin analogs, finding that silicone CLs were more effective in releasing agomelatine and 5-MCA-NAT compared to conventional materials. Preloaded CLs triggered higher tear secretion in rabbits than corresponding eye drops, suggesting their potential as an effective strategy for managing dry eye disease [ 49 ].…”

“…In summary, melatonin and its analogs hold promise as therapeutic agents for DED. Their potential benefits include modulating the corneal hydration state, increasing tear secretion, and protecting against ROS-induced inflammation [ 49 ]. Further studies employing a multi-level strategy utilizing a combination of melatonin and its analogs acting on distinct receptors are warranted to optimize DED management.…”

Updates on Biodegradable Formulations for Ocular Drug Delivery

“…Encapsulating the drug in nanocapsules or nanomicelles prior to embedding them in punctal plugs has been explored to improve drug delivery efficacy [ 92 , 93 ]. Contact lenses provide an alternative for ocular surface diseases treatment by immersing the lenses in a drug solution, but rapid drug release and visual acuity issues are associated with this method [ 94 , 95 , 96 ]. Ring-implanted contact lenses that encapsulate drugs within NPs and deliver them through a ring-shaped boundary region have been developed to mitigate these issues.…”