pH triggered controlled drug delivery from contact lenses: Addressing the challenges of drug leaching during sterilization and storage

In the present work a novel cyclosporine-loaded Eudragit S100 (pH-sensitive) nanoparticles-laden contact lenses were designed to provide sustained release of cyclosporine at therapeutic rates, without leaching of drug during sterilization and storage period (shelf life). The nanoparticles were prepared by Quasi-emulsion solvent diffusion technique using different weight ratios of cyclosporine to Eudragit S100. The contact lenses with direct drug entrapment were also fabricated (DL-50) for comparison. The percentage swelling and optical transparency of nanoparticles-laden contact lenses were improved in comparison to DL-50 lenses. The nanoparticles-laden contact lenses showed sustained drug release profiles, with inverse relationship to the amount of nanoparticles loaded in the contact lenses. It was interesting to note that nanoparticles form nanochannels/cavities after dissolution of Eudragit S 100 in tear fluid pH = 7.4 (in vitro release study). This followed the precipitation of drug in hydrogel matrix of contact lenses. As the amount of nanoparticles loading increased, more number of cavities were formed, which caused the formation of large cavities in contact lens matrix. This in turn precipitated the drug. The nanoparticles-laden contact lenses with 1:1 (drug: Eudragit) weight ratio showed the most promising results of sustaining the drug release up to 156 h, without affecting optical and physical properties of contact lenses. Packaging study confirmed that the drug was not leached in packaging solution (buffer, pH = 6.5) from nanoparticles-laden lenses during shelf life period. In-vivo study in rabbit tear fluid showed sustained release up to 14 days. The study revealed the application of pH-sensitive nanoparticles-laden contact lenses for controlled release of cyclosporine without altering the optical and physical properties of lens material. (C) 2017 Elsevier B.V. All rights reserved.