Rosmarinic acid-eluting contact lenses as a multifunctional therapeutic system for diabetic ocular complications

Drug-eluting contact lenses (CLs) offer a promising approach to treat diabetic eye diseases. Compared to conventional treatments such as eye drops, CLs enhance drug bioavailability and residence time on the eye, while addressing patient compliance issues. Additionally, CLs are a safer alternative to ocular injections. In this study, CLs were designed for the sustained release of rosmarinic acid (RA), a natural polyphenol known for its antioxidant, anti-inflammatory, antibacterial and neuroprotective properties, which has been proposed as an alternative therapy for diabetic ocular complications. Acrylic and silicone-based hydrogels were produced and pre-treated with vitamin E. A sustained release of RA for up to 24 h was achieved under hydrodynamic conditions, which is compatible with the use of this hydrogel as daily CLs. Comprehensive characterization confirmed that the hydrogel's physicochemical properties met commercial CLs standards, while no signs of ocular irritation nor cytotoxicity were observed in vitro. Ex vivo studies demonstrated that the drug could permeate through ocular tissues. The ocular RA distribution after the CL application was estimated in silico. Finally, the neuroprotective effect of RA was evaluated ex vivo in porcine retinal explants, confirming the therapeutic relevance of the designed hydrogels in the treatment of the diabetic eye.