Chau-Minh Phan, MA is working on a PhD at the Centre for Contact Lens Research, University of Waterloo. His work involves developing ocular drug delivery materials (contact lenses and nanoparticles) for antifungals.Notably, approximately half of contact lens wearers in North America report symptoms of dryness and discomfort at the end of the day. The discomfort experienced with contact lens wear is one of the primary reasons leading to their discontinued use1. Commercially available cyclosporine A emulsion eye drops (Restasis®, Allergan) containing 0.05% cyclosporine A can be used to alleviate these dry eye related symptoms. Cyclosporine A acts as an immunosuppressant to reduce inflammation in the eyes and tear-producing glands, leading to higher tear production. However, like most eye drop formulations, it suffers from low drug bioavailability as a result of nonspecific drainage and absorption through the trans-nasal and conjunctival route. Less than 5% of the drug reaches the intended target site. The use of eye drops is also inconvenient, requiring lens wearers to remove their lenses prior to instilling the drops and then re-insert them after 15 minutes. In the following overview, Chau-Minh Pham reviews a novel 2011 study conducted by Peng and Chauhan, which demonstrated that cyclosporine A can be incorporated and released from commercially available silicone hydrogel contact lenses to treat contact lens-mediated and chronic dry eye.
Peng CC, Chauhan A. Extended Cyclosporine delivery by silicone-hydrogel contact lenses. Journal of Controlled Release 2011; 154: 267-274
About the study
Five contact lenses, 1-DAY ACUVUE®, ACUVUE® OASYS™, NIGHT&DAY™, O2OPTIX™ and PureVision™ were examined in this study. These lenses were loaded with cyclosporine A by simple incubation in a cyclosporine A-phosphate buffered saline (PBS) solution for seven days. The release of the drug in PBS was monitored using UV-VIS spectrophotometry between 208-220nm. Another set of ACUVUE® OASYS™ lenses were also soaked with Vitamin E-ethanol solution for 24 hours, resulting in a 20% Vitamin E loaded lens, prior to cyclosporine A loading. A previous study has shown that Vitamin E soaked lenses have improved sustained drug release.2
Drug release time
The release of cyclosporine A from 1-DAY ACUVUE®, a conventional hydrogel lens, was 24 hours. This release duration is adequate considering that it is a daily disposable lens.
Silicone hydrogel contact lenses (ACUVUE® OASYS™, NIGHT&DAY™, O2OPTIX™, and PureVision™) had extended drug release periods–more than seven days.
ACUVUE® OASYS™ lenses soaked with Vitamin E were able to release cyclosporine A for over a month. Vitamin E loading also reduced variation in the rate of drug release over time.
Effect on refractive index of the lenses
The loading of cyclosporine A into the lenses had a minimal effect on the refractive index of the lenses. ACUVUE® OASYS™ lenses loaded with 20% Vitamin E, however, had a significant increase in refractive index. This change can be accommodated by simply changing the refractive index of the original lens such that the refractive index of the loaded lens will meet the patient’s prescription.
Delivery of cyclosporine A: drops vs. contact lenses
Cyclosporine A eye drops are typically used twice a day for the treatment of moderate dry eye. While 28 µg/day of drug is delivered through these droplets, only 2.8% of the drug (0.78 µg/day) will reach the cornea and conjunctiva. Clinical studies have shown that administration of an increase in drug concentration up to eight-fold (224 µg/day) has no toxic side effects, but there are also no additional benefits. Delivering cyclosporine A through contact lenses will result in higher drug bioavailability due to increased residence time of the drug in tears, with an estimated 50% of the released drug reaching its intended site. Based on this model, a release between 1.6µg/day to 12.8 µg/day of cyclosporine A by contact lenses should provide therapeutic drug levels equivalent to that delivered via eye drops.
Conclusion
1-DAY ACUVUE® was capable of releasing therapeutic levels of cyclosporine A for a one-day period. ACUVUE® OASYS™, NIGHT&DAY™, O2OPTIX™ and PureVision™ were able to maintain therapeutic delivery rates for 14 days. The duration cannot be increased any further without causing toxicity in the initial release periods. ACUVUE® OASYS™ loaded with 20% Vitamin E was able to release cyclosporine A within the therapeutic regions for up to 20 days, which can be increased up to a month by increasing the concentration of drug-loading solution.
While in vivo release and toxicity studies still need to be conducted to fully evaluate the benefits of cyclosporine A release from contact lenses, this study nonetheless demonstrates a promising and readily available solution for treating contact lens-mediated and chronic dry eyes.
References:
1. Fonn D, Dumbleton K. Dryness and discomfort with silicone hydrogel contact lenses. Eye Contact Lens 2003; 29(1 Suppl): S101-104; discussion S115-108, S192-104.
2. Peng CC, Kim J, Chauhan A. Extended delivery of hydrophilic drugs from silicone-hydrogel contact lenses containing vitamin E diffusion barriers. Biomaterials 2010; 31(14): 4032-4047.
