Nanoelectrospray fabrication of pH-responsive double-layered drug-eluting contact lenses for ocular drug delivery

Additive manufacturing approaches enable the rapid production of drug-eluting contact lenses (DECLs) directly from commercially available lenses. Nanoelectrospraying (nES) is a promising additive technique, capable of applying drug coatings within seconds per lens. However, DECLs made by nES share similar challenges to DECLs made by other methods, including minimising drug loss into the packaging solution and achieving controlled drug release. In this study, bimatoprost, a drug widely used in glaucoma therapy, was selected as a model compound to develop a double-layered, pH-responsive DECL system incorporating drug-loaded NPs. The bimatoprost-loaded NPs were prepared using flash nanoprecipitation with zein and hyaluronic acid (HA). They were characterised for size, zeta potential, and entrapment efficiency. A double-layer coating was applied using nES, with the base layer comprising NPs in polyvinyl alcohol (PVA) and the top layer using Eudragit L100 for pH-responsive drug release. DECLs were evaluated for coating uniformity, optical transmittance, and storage stability. Comparative in vitro drug release studies were performed under static conditions and with a custom 3D-printed tear flow simulating device (TFS) to simulate physiological tear dynamics. Bimatoprost-loaded NPs exhibited a reasonable colloidal stability and entrapment efficiency. Drug release from soaked lenses (as the control sample) or nES single-layer-coated lenses was rapid, highlighting the need for advanced coating approaches. Storage stability studies confirmed drug retention of the DECLs with the double-layer coating, with minimal loss over storage at pH 5.5. Under physiological pH (pH 7.4), sustained drug release was achieved, demonstrating a 34% reduction in burst release and a significant increase in sustained release to single-layer coatings and soaked lenses. In conclusion, the double-layered, nanoparticle-loaded DECLs with a pH-responsive coating effectively demonstrated sustained drug release at physiological pH, with significantly reduced drug loss during storage in packaging solution. This scalable platform has the potential for DECL manufacturing which provides an alternative ocular drug delivery solution for chronic conditions like glaucoma.