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Epalrestat-loaded silicone hydrogels as contact lenses to address diabetic-eye complications.
Most treatments for diabetic eye conditions rely on systemic (oral) or intravitreal administration, and there is still a demand of efficient and comfortable ocular dosage forms. Our purpose was to design contact lenses (CLs) suitable for local prophylaxis/treatment of diabetes-related ocular pathologies, by means of the incorporation of bioinspired functional groups that can reversibly interact with epalrestat, an aldose reductase inhibitor. Several sets of silicone hydrogels were synthesized varying the contents in 2-hydroxyethyl methacrylate (HEMA), monomethacryloxypropyl-sym-polydimethylsiloxane hydroxypropyl terminated (MCS-MC12), and aminopropyl methacrylamide (APMA). Epalrestat was incorporated before or after polymerization, and loading and release profiles compared. All sets were evaluated regarding optical properties, oxygen permeability, swelling, cytocompatibility, ocular irritation, and corneal drug penetration (using a drug solution as reference). Designed silicone hydrogels showed adequate properties to be used as CLs. Affinity for epalrestat strongly depended on the content in APMA, which endowed the hydrogels with prolonged release in 0.9% NaCl for one week, both after synthesis and after being re-loaded. Bovine corneal permeability tests demonstrated that epalrestat released from the hydrogels can efficiently accumulate into the cornea in spite the concentrations provided on cornea surface were lower than those attained after instillation of concentrated eyedrops. Epalrestat-loaded hydrogels also demonstrated anti-cataract activity in an in vitro model of diabetic eye. Overall, silicone hydrogel CLs functionalized with bioinspired chemical groups represent a first attempt to design CLs adapted to the needs of diabetic eyes, acting as controlled release platforms of epalrestat, promoting drug accumulation and diffusion through cornea.
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