NVP-based molecularly imprinted hydrogel contact lenses for sustained delivery of Naringenin: In vitro, Ex vivo, cytocompatibility, anti-inflammatory and ISO standardized physicochemical evaluation

Abstract

Naringenin (NAR), due to poor aqueous solubility, faces hindrances in clinical applications to prevent eye diseases such as age-related macular degeneration (AMD). Herein, molecularly imprinted (MiF) contact lenses were fabricated for sustained NAR release and improved corneal and scleral permeability. NAR-imprinted MiF lenses were manufactured employing injection molding and thermal polymerization approach and were characterised according to ISO standards. Template removal, NAR competitive reloading, in vitro release, ex vivo porcine corneal and scleral permeation and in vitro biocompatibility assays were performed. Fabricated MiF lenses showed 74 − 78 % water content, 1.373 ± 0.002 refractive index, >95 % optical transparency, contact angle of 44.4 ± 0.3° and Young's moduli of 0.69 ± 0.08 MPa. Molecular docking (MD) showed strong interactions between NAR and hydrogel matrix (Biotrue® monomer mixture). NAR loading of 40–50 μg/mg of dry MiF lenses with 3.8–4.2 imprinting factor was measured with significantly greater NAR selectivity (p < 0.05) towards imprinted cavities over quercetin (QCN) − analogous to NAR. MiF lenses showed 50 − 63 % sustained NAR in vitro release over 120 h, followed by ex vivo corneal and scleral accumulation of 6.10 ± 1.4 to 14.63 ± 1.8 μg/cm², respectively. Immortalized human corneal epithelial cells (IM-HCEpiC) and adult retinal pigment epithelium (ARPE-19) cell-focused cytocompatibility and anti-inflammatory studies demonstrated strong clinical and commercialization potential of developed MiF lenses for ocular applications.