Enhanced Ocular Delivery of Epalrestat Using Nanostructured Lipid Carrier Laden Soft Contact Lens.

Background/Objectives: Epalrestat (EPL), an aldose reductase inhibitor, exhibits poor aqueous solubility and limited ocular bioavailability, which significantly restricts its therapeutic efficacy in the treatment of diabetic retinopathy. To overcome these limitations, a novel nanostructured lipid carrier (NLCs)-laden contact lens system was developed to achieve sustained and enhanced ocular delivery of EPL. Methods: In this study EPL-loaded NLCs were prepared using Compritol® 888 ATO (solid lipid), Labrafac™ WL 1349 (liquid lipid), and Solutol® HS 15 (surfactant) using high-speed homogenization method. The formulations were statistically optimized using a D-optimal mixture design, considering globule size (Y1), swelling index (Y2), and drug release at 6 h (Y3) as key responses. The optimized NLCs were incorporated into contact lenses via the soaking technique and evaluated for physicochemical properties, drug content, in vitro release, ex vivo corneal permeability, and in vivo ocular tolerance. Results: The optimized NLCs formulation showed a globule size of 41.85 ± 2.14 nm, zeta potential of -20.3 ± 1.8 mV, and entrapment efficiency of 93.32 ± 1.27%, indicating excellent physical stability with high drug encapsulation. The swelling index of the optimized NLCs-laden contact lens was 140.69 ± 4.32%, and the optical transmittance was 80.54 ± 1.12%, confirming adequate hydration and transparency for ocular use. The drug content was 96.32 ± 0.84%, ensuring uniform distribution throughout the hydrogel matrix. In vitro release studies demonstrated a sustained drug release of 98.12 ± 2.08% over 24 h, whereas ex vivo corneal permeation indicated significantly higher permeation (97.26 ± 1.95% at 6 h) compared with the control contact lens (38.14 ± 2.41% at 5 h). The in vivo Draize test confirmed that both blank and drug-loaded contact lenses were non-irritating and biocompatible. Conclusions: Thus, the optimized EPL NLCs-laden contact lens demonstrated enhanced corneal permeation, prolonged drug retention, and excellent ocular safety, offering a promising advancement in the management of diabetic retinopathy by improving bioavailability, reducing dosing frequency, and enhancing therapeutic efficacy.