Tobramycin-laden 3D-printed UV-cured hyaluronic acid-PVA-based contact lens-like patches for improved antibiofilm activity and corneal healing in bacterial keratitis.

Delivering therapeutic agents through 3D-printed contact lenses like patches (CLLPs) is a promising strategy to achieve notable bioavailability while minimizing ocular drainage. In this study, 3D-printed CLLPs (15 mm in diameter, 0.3 mm in thickness, and 4 mm in height) were fabricated using a unique combination of polyvinyl alcohol methacrylate (PVAMA) and hyaluronic acid methacrylate (HAMA) in an optimal ratio, which was further UV-crosslinked (365 nm) and loaded with tobramycin to form a drug-eluting contact lens-like patch to relief bacterial keratitis (BK). The bio-ink utilized for 3D printing exhibited excellent mechanical properties and viscosity. The TOB@PVAHA 2 % CLLPs demonstrated enhanced permeation through corneal tissue and sustained drug release. The 3D-printed contact lenses like patches displayed good mucoadhesive properties, wettability, transparency, and a favorable swelling index. Furthermore, the TOB@PVAHA 2 % CLLPs exhibited significant antibacterial activity, as evidenced by minimum inhibitory concentration (MIC), zone of inhibition, colony counting assay, live/dead assay, and antibiofilm activity against BK-causing pathogen Pseudomonas aeruginosa. In vivo studies in a rabbit model of bacterial keratitis demonstrated a significant reduction in bacterial load following treatment with TOB@PVAHA 2 % CLLPs. The immunostaining of corneal tissues revealed the downregulation of inflammatory cytokines after treatment with TOB@PVAHA 2 % CLLPs. Overall, the newly developed delivery system could disrupt matured biofilms, enhance corneal retention time, and provide high bioavailability of loaded drug. The drug-eluting dissolvable CLLPs could potentially be a clinically translatable vision-restoration strategy for treating advanced stages of BK.