Engineering Mixed Micelle-Loaded Contact Lenses for Sustained Ocular Delivery of Dexamethasone: In Vitro and In Vivo Studies.

Conventional dexamethasone eye drops suffer from poor ocular bioavailability due to rapid tear turnover and limited corneal residence, necessitating frequent dosing and posing challenges in chronic ocular therapies. This study addresses the need for a sustained and biocompatible ocular delivery platform by engineering hydrogel contact lenses incorporating dual-surfactant micelles for prolonged dexamethasone release. Micelles were prepared using Pluronic P123 and TPGS at different weight ratios, with a total surfactant concentration of 0.1% w/v─ten times above their critical micelle concentration─to optimize drug solubilization and encapsulation. DLS confirmed nanoscale micelles (∼11-14 nm) with a narrow size distribution. Compared to conventional soaking and single-surfactant systems, mixed micelle-laden lenses achieved significantly higher drug loading (59.1  ±  11.5 μg), minimized leaching during sterilization, and reduced burst release. In vitro release extended over 96 h with sustained flux. In vivo studies in rabbits demonstrated a >20-fold improvement in bioavailability (AUC0-24 = 579 μg·h/mL) and extended mean residence time (8.8 h) compared to eye drops, maintaining therapeutic tear concentrations for 24 h postapplication. The formulation also suppressed inflammatory IL-6 levels to near baseline, outperforming eye drops and soaked lenses. Cytotoxicity (96.3% viability) and ocular irritation tests confirmed excellent biocompatibility. In conclusion, this dual-surfactant micelle platform markedly enhances the therapeutic potential of drug-eluting contact lenses, offering a safe, sustained, and patient-compliant alternative for managing ocular inflammation. These findings support further clinical translation of micelle-integrated lenses as next-generation ocular drug delivery systems.