A promising ‘single’ and ‘dual’ drug-nanocomposite enriched contact lens for the management of glaucoma in response to the tear fluid enzyme

Abstract

Glaucoma is a neurodegenerative condition that results in the damage of retinal ganglion cells due to elevated intraocular pressure (IOP). To curtail the limitations associated with conventional treatments such as eye drops and ocular suspensions, we have developed ‘single’ and ‘dual’ drug delivery contact lenses (CLs), that is, latanoprost (LP) and latanoprost-timolol (LP-TM) deliverable CLs, in response to lysozyme (Lyz), which is abundant in the lacrimal fluid. Since chitosan (CS) can entrap more of the drug and also undergo hydrolysis in the presence of Lyz, we have employed CS for the composite preparation. The CL fabrication was performed by free radical copolymerization of poly(2-hydroxyethyl methacrylate) (pHEMA) in the presence of the drug-loaded nanocomposite with UV-curing initiators using the pre-drug loading strategy. The surface morphological, optical and mechanical investigations confirmed the presence of the drugs, ≥80% transparency, the adequate flexibility and biocompatibility of both the CLs. The in vitro release experiments showed the release of 95.86% LP from LP-CL, and 83.87% LP and 86.70% TM from LP-TM-CL in the presence of 1.5 mg mL⁻¹ of Lyz in 72 h. In vitro biocompatibility assay against human corneal epithelial (HCE) cells and ex vivo experiments on HET-CAM confirmed that the fabricated LP-CL and LP-TM-CL are well tolerated. Moreover, in vivo safety evaluations of CLs on New Zealand white rabbit eyes suggest no sign of irritation to the ocular tissues within 72 h of observation. Hence, the study suggests that the ‘single’ and ‘dual’ drug-loaded CLs could open a new avenue to manage glaucoma by maintaining mean diurnal IOP.