Lifitegrast-eluting contact lens for dry eye disease: sustained release, enhanced ocular bioavailability, and robust in vitro-in vivo correlation.

Dry eye disease (DED) severely impacts patients' quality of life. Conventional treatments like lifitegrast eye drops face challenges of low bioavailability and adverse effects. This study developed lifitegrast-eluting contact lenses (DeCLs) to enhance ocular drug delivery. Three DeCLs formulations (DeCLs-1: 0.2 mg, DeCLs-2: 0.3 mg, DeCLs-3: 0.6 mg) were prepared via soaking method. In vitro release studies using artificial tears flowing through a microfluidic chamber at controlled rates (0.15 ~ 0.30 mL/min) demonstrated sustained drug release profiles that were dependent on the flow rate. Functional evaluations confirmed DeCLs maintained optical clarity, diopter, mechanical integrity, and ion permeability comparable to blank lenses, with no significant swelling changes. Ex vivo studies in rabbit eyes revealed 50 ~ 60% cumulative drug release over 8 h, with DeCLs-2 following zero-order kinetics (R = 0.99725). At a dosage of 0.3 mg, DeCLs demonstrated comparable tear exposure (AUC) to that of eye drops administered at a dose of 1.0 mg. In vivo pharmacokinetics showed prolonged mean residence time of the DeCLs versus eye drops (p < 0.01), alongside reduced peak-to-trough fluctuations (> 99% lower). When the flow rate in the microchamber was set at 0.15 mL/min, DeCLs-1, DeCLs-2, and DeCLs-3-particularly DeCLs-2-demonstrated excellent in vitro-in vivo correlation (r = 1.00000). These findings demonstrate that DeCLs represent a promising therapeutic approach for DED, providing sustained drug delivery, reduced side effects, and improved patient compliance. Furthermore, the novel in vitro release model developed in this study, which establishes strong in vitro-in vivo correlation, paves the way for more ethical pharmaceutical research by potentially reducing reliance on animal testing.