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.

In vitro and in vivo evaluation of novel implantation technology in hydrogel contact lenses for controlled drug delivery.

Glaucoma is commonly treated using eye drops, which is highly inefficient due to rapid clearance (low residence time) from ocular surface. Contact lenses are ideally suited for controlled drug delivery to cornea, but incorporation of any drug loaded particulate system (formulation) affect the optical and physical property of contact lenses. The objective of the present work was to implant timolol maleate (TM) loaded ethyl cellulose nanoparticle-laden ring in hydrogel contact lenses that could provide controlled drug delivery at therapeutic rates without compromising critical lens properties. TM-implant lenses were developed, by dispersing TM encapsulated ethyl cellulose nanoparticles in acrylate hydrogel (fabricated as ring implant) and implanted the same in hydrogel contact lenses (sandwich system). The TM-ethyl cellulose nanoparticles were prepared by double emulsion method at different ratios of TM to ethyl cellulose. The X-ray diffraction studies revealed the transformation of TM to amorphous state. In vitro release kinetic data showed sustained drug release within the therapeutic window for 168h (NP 1:3 batch) with 150µg loading. Cytotoxicity and ocular irritation study demonstrated the safety of TM-implant contact lenses. In vivo pharmacokinetic studies in rabbit tear fluid showed significant increase in mean residence time (MRT) and area under curve (AUC), with TM-implant contact lenses in comparison to eye drop therapy. In vivo pharmacodynamic data in rabbit model showed sustained reduction in intra ocular pressure for 192h. The study demonstrated the promising potential of implantation technology to treat glaucoma using contact lenses, and could serve as a platform for other ocular diseases.