In vitro and in vivo evaluation of ketotifen-gold nanoparticles laden contact lens for controlled drug delivery to manage conjunctivitis

Abstract

To overcome the limitations of eye drop solutions, contact lenses are widely used for controlled ophthalmic drug delivery. However, drug-laden contact lenses prepared by traditional soaking technique show poor drug uptake, high burst release, and altered critical lens properties. In the current paper, the effect of gold nanoparticles (GNPs) on ketotifen uptake from the drug-soaking solution and its release kinetics from the lens was investigated. In one method, GNPs solutions of varying strength were loaded into the ketotifen-soaking solution (mM-GNPs-SS batches), and in another method, the GNPs were incorporated in the contact lens during fabrication (mM-GNPs-L batches). The GNPs were spherical, with an average diameter of 17.2 nm and a zeta potential of −21.2 mV. The contact lens's swelling, oxygen permeability, and optical transmittance were improved when compared to lenses prepared by traditional soaking method (K-SM-L). The mM-GNPs-L lenses showed substantial improvement in drug uptake from the ketotifen-soaking solution compared to the K-SM-L and mM-GNPs-SS lenses. The in vitro experiments showed low burst and control ketotifen release up to 96 h, compared to 48 h with the K-SM-L lens. The ability to sustain ketotifen release profile improved proportionally with an increase in the amount of GNPs in the lens. The protein adherence was reduced with the presence of GNPs in the contact lens. The GNPs-laden lenses were found to be safe in ocular irritation and histopathology reports (rabbit model). Further, they showed higher ketotifen retention in the rabbit tear fluid compared to the K-SM-L lens and eye drop solution. Thus, the presence of GNPs in contact lenses increased ketotifen uptake from the soaking solution, reduced burst release, and improved the in vitro and in vivo release kinetics without affecting the critical lens properties for therapeutic application.