Cyclodextrin-based therapeutic contact lenses for improved nepafenac bioavailability

Recovery after cataract surgery in diabetic patients can be compromised by postoperative inflammation and macular edema, creating a need for sustained and patient-friendly anti-inflammatory ocular delivery strategies. Contact lenses (CLs) are promising ocular drug-delivery platforms that can overcome the short residence time and patient discomfort associated with frequent instillation of ophthalmic suspensions. Here, we developed acrylic- and silicone-based hydrogel CL materials containing varying amounts of hydroxypropyl-β-cyclodextrin (HP-β-CD) to enhance affinity for nepafenac, a poorly soluble nonsteroidal anti-inflammatory drug widely prescribed to reduce postoperative inflammation and help prevent macular edema. Hydrogel performance relevant to CL use (swelling, optical transmittance, and ionic permeability) was assessed. Nepafenac was loaded by soaking the hydrogels in a drug suspension, and steam sterilization was exploited as a functional processing step that promoted nepafenac: HP-β-CD inclusion complexation within the network. Drug release was evaluated under static sink conditions and under tear-like hydrodynamic conditions using a microfluidic cell that mimics ocular functioning. Biocompatibility was assessed through corneal epithelial cell cytocompatibility and HET-CAM irritation tests, and ex vivo permeation across porcine ocular tissues was investigated. HP-β-CD–functionalized silicone hydrogels maintained suitable key CL properties and increased nepafenac uptake by up to 2.5-fold after autoclaving, enabling sustained release for more than 24 h. This effect is consistent with enhanced nepafenac solubilization and drug–HP-β-CD association during loading, although direct confirmation of complex formation within the hydrogel network will require further studies. The materials were non-cytotoxic and non-irritant and enhanced nepafenac transport across corneal and scleral tissues. Overall, the developed nepafenac-eluting silicone hydrogels represent a promising CL-based platform for sustained ocular delivery of nepafenac and a potential alternative to conventional eye drops.