(M1330-12-80) Development of a Novel Therapeutic Contact Lens with the Embedded-Drug Chamber as an Ophthalmic Drug Delivery System for Dry Eye Syndrome

Purpose: Eye drops are used to treat dry eye syndrome, but it has very low bioavailability, only less than 5% of the dose in eye drops is absorbed, and the therapeutic duration is not sustained due to precorneal elimination factors. To improve the bioavailability and therapeutic duration, therapeutic contact lenses were developed. However, the previously developed therapeutic contact lenses have limitations such as high burst release, short release duration, and change in contact lens characteristics. It needs to overcome the limitation of previously developed therapeutic contact lenses to achieve an effective ophthalmic drug delivery system using therapeutic contact lenses. This study aimed to develop novel therapeutic contact lenses to overcome the limitation of previously developed therapeutic contact lenses and to enhance the therapeutic performance of lifitegrast.

Methods: The novel contact lens was prepared using the mold casting method, and it consists of drug chambers and drug release channels and is designed to store a drug in the drug chamber and release the drug through a drug release channel. The 2-hydroxyethyl methacrylate (HEMA) was used as lens material, and the geometric chamber layer and blocking layer were produced by pouring 2-HEMA into customized molds. As bonding two layers by plasma, the novel contact lens was produced. The novel therapeutic contact lens evaluated the physicochemical properties such as transmittance, oxygen transmissibility, and Young’s modulus. To develop a lifitegrast formulation, the experiment (DoE) was designed with a Box-Behnken design. As the independent variables Carbomer, hydroxypropyl methylcellulose (HPMC), and poloxamer were used. The formulation was optimized by derived design space with a 1% failure probability. The optimized formulation was loaded into the novel therapeutic contact lens and evaluated for various physicochemical properties, such as assay, in vitro drug release, and ex vivo trans corneal permeation.

Results: To assure the comfort and quality of contact lenses, the physicochemical properties of novel therapeutic contact lenses were evaluated. As a result, transmittance, oxygen transmissibility, and Young’s modulus were above 90%, 37 DK/t, and 0.75 Mpa, respectively, within the range of commercial contact lenses. To optimize lifitegrast formulation, a Monte Carlo simulation was performed, and a robust design space with a 1% failure probability was established. The optimized formulation was 0.5mg/mL of HPMC in a robust design space. The optimized formulation was loaded into the contact lens and evaluated the assay, in vitro drug release, and ex vivo trans corneal permeation. As a result, the novel contact lenses which loaded the drug showed 99.94±3.16% of an assay; it satisfied the assay criteria (above 95%). In addition, in vitro drug release overcame the limitation of previously developed therapeutic contact lenses by decreasing the initial burst release and extending the drug residence time in the eyeball by maintaining sustained drug release for up to 6h (90.35±0.77% at 6h). As a result of ex vivo trans corneal permeation, the cumulative amount of lifitegrast permeated across rabbit cornea from the novel contact lens showed 52.88±0.32% at 6h, which satisfied the criteria of the ex vivo trans corneal permeation (above 50%).

Conclusion: In this study, the potential of a novel therapeutic contact lens with the embedded drug chamber to enhance the therapeutic performance of lifitegrast was investigated. The novel therapeutic contact lens ensured comfort and quality since it showed physicochemical properties within the range of commercial contact lenses. The formulation of the drug solution optimized by the DoE was loaded into the novel contact lens, and it satisfied the criteria of the assay, in vitro drug release, and ex vivo trans corneal permeation. Moreover, it showed an appropriate drug release profile, decreasing initial burst release and extending the drug residence time. Our findings showed that the novel therapeutic contact lenses could overcome the limitation of previously developed lenses and eye drops and enhance the therapeutic performance of lifitegrast.

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).

Fig. 1. Schematic diagram of this study

Fig. 2. Result of physicochemical properties of contact lens. (a) Transmittance, (b) Oxygen transmissibility, and (c) Young’s modulus.

Fig. 3. Result of contact lens which loaded optimized lifitegrast formulation. (a) Assay, (b) In vitro drug release, and (c) Ex vivo trans corneal permeation.