(M1030-12-80) Enhanced Ocular Delivery of lifitegrast Using New Contact Lens DDS System

Purpose: In general, ophthalmic administered drug shows poor bioavailability of less than 5% due to the presence of corneal epithelial barrier and short retention in precorneal site. Thus, many eye drop formulations have therapeutic limitations such as high inter-individual variability of PKPD, low drug compliance, and insufficient drug efficacy. In the present study, we aimed to evaluate the impact on pharmacokinetics of a new contact lens ocular drug delivery system that extends the precorneal residence using lifitegrast as a model drug.

Methods: The New Zealand white rabbits were used for pharmacokinetic characterization of lifitegrast. Xiidra^Ⓡ, which is a marketed eye drop formulation, was administered at a dose of 2.5 mg/eye (50 μL/eye) as an reference. In test groups, respective two types of IR and SR contact lenses containing 1.25 mg of lifitegrast were administered. At 6 h following administration, the lens was removed. Plasma and ocular tissues including cornea, conjunctiva, aqueous humor, vitreous humor, retina, iris, and crystalline lens were collected at predetermined sampling points. The remaining lifitegrast in collected lenses were also determined to estimate the drug dissolution profiles in rabbits.

Results: In the reference group, maximum concentration of lifitegrast (C_max) in the plasma, cornea, and conjunctiva was reached at 0.25 h after dosing. In the IR lens group, T_max of plasma, cornea, and conjunctiva were observed at 0.44, 1, and 0.5 h following administration. Compared to reference group, the dose-normalized AUCs of the ocular tissues were increased about 7 to 350 times. In the SR lens administered group, lifitegrast reached to C_max at 0.25, 4, and 0.25 h in the plasma, cornea, and conjunctiva, respectively. Ocular drug delivery increased 4 to 120 times compared to reference dosed group. The highest tissue concentration was observed for the cornea followed by the conjunctiva, aqueous humor, iris, sclera, retina, vitreous humor, and crystalline lens. Also, 65-80% of loaded lifitegrast in SR lens were released for 4 h after drug administration.

Conclusion: In the present study, the impact on ocular pharmacokinetics of prolonged drug retention in the precorneal area by contact lenses was evaluated. The new lifitegrast DDS system with the contact lenses greatly improved ocular bioavailability.

Acknowledgements: This research was supported by the Industrial Strategic Technology Development Program (20008799, Development of drug delivery application technology using contact lenses to increase the absorption rate of dry eye treatment drug (lifitegrast)), funded by the Ministry of Trade, Industry, and Energy (MOTIE, Korea).