Co-delivery of timolol and hyaluronic acid from semi-circular ring-implanted contact lenses for the treatment of glaucoma: in vitro and in vivo evaluation.

Glaucoma is a chronic disease, which is currently treated using frequent high dose applications of an eye drop solution; this method is tedious, and most of patients are non-compliant to it. Contact lenses are emerging as a convenient option to sustain the release of ophthalmic drugs. However, the incorporation of a drug/formulation changes the optical and physical properties of contact lenses. Contact lens users have also reported pink eye syndrome; this makes contact lenses unsuitable to be accepted as a medical device. The objective of the present study was to design novel timolol and hyaluronic acid (comfort agent)-loaded semi-circular ring-implanted contact lenses that could uphold the release at therapeutic rates without compromising the critical lens properties. The drug-loaded rings were individually implanted within the periphery of the contact lenses using modified cast-moulding technology. Atomic force microscopy showed an average roughness of 12.38 nm for the implanted lens that was significantly lower as compared to that of the Freshlook contact lenses (116.27 nm). A major amount of timolol was leached (from 46.47 to 58.79%) during the monomer extraction and moist sterilization (autoclave) steps; therefore, the lenses were sterilized by radiation and packaged under dry conditions (dehydrated). The in vitro release data showed sustained release of timolol and hyaluronic acid up to 96 h. The in vivo drug release study on rabbit eyes showed the presence of timolol in tear fluid up to 72 h. The in vivo pharmacodynamics studies showed a reduction in IOP till 144 h with a low drug loading (154 µg) as compared to the case of a single instillation eye drop solution (250 µg). This study has demonstrated the successful application of implantation technology to co-deliver timolol and hyaluronic acid from contact lenses for an extended period of time to treat glaucoma.

Design and optimization of a novel implantation technology in contact lenses for the treatment of dry eye syndrome: In vitro and in vivo evaluation.

Contact lenses are widely used for ophthalmic drug delivery, but incorporation of drug or formulation in the contact lenses affects its optical and physical property. In the present study, we have designed a novel hyaluronic acid (HA)-laden ring implant contact lenses (modified cast moulding method), to circumvent the changes in critical lens property. The objective was to improve the ocular residence time of HA, by providing sustained ocular HA delivery through implant contact lenses for the treatment of dry eye syndrome. Optimization of HA-implant was carried out using 32 factorial design by tailoring the amount of cross linker and thickness of implant, to achieve sustained HA release with constraint on effective ion diffusivity. The in vivo pharmacokinetic study in rabbit tear fluid showed sustained HA release up to 15days, by fabricating implant (80µgHA loading) with 78.4µm thickness (total thickness of lens=100µm) using 0.925% of cross linker, with effective ion diffusivity>1.5×10-6mm2/min. In vivo efficacy study in benzalkonium chloride induced dry eye syndrome rabbits showed faster healing with implant contact lenses in comparison to positive control group. The study demonstrated the promising potential of implantation technology to deliver hyaluronic acid without compromising optical and physical properties of contact lens. STATEMENT OF SIGNIFICANCE: The limitation of contact lenses to be used as therapeutic device for controlled drug delivery is focused in this study. Incorporation of drug or formulation in the biomaterial affects the optical and physical property of contact lenses. The significance of project was to design a novel hyaluronic acid-laden ring implant contact lenses, to by-pass the changes in critical property of biomaterial.