Sustained delivery technology for Cyclosporine A in the treatment of autoimmune response

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PROJECT SUMMARY Sixteen million Americans are diagnosed with dry eye disease, with likely many more suffering from this issue. Prevalence is higher among women, increases with age, and is now also notable among those aged 18–34 years. It is characterized by a loss of homeostasis of the tear film and may be accompanied by persistent symptoms of irritation or burning that can cause inflammatory damage to the cornea and conjunctiva if untreated. Current eye-drop treatments that work by reducing the inflammation on the ocular service have several deficiencies that can be frustrating for patients. The immunomodulator, cyclosporine, is commonly prescribed in these eye drops using a variety of delivery vehicles including anionic emulsions, cationic nanoemulsions, or nanomicellar solutions. However, the impact of the vehicle to prolong corneal residence is still limited due to natural ocular defensive mechanisms. This is believed to be one reason that the common dry eye disease treatment by such eye drops do not have better or faster efficacy in clinical trials. The project team proposes to incorporate cyclosporine into a contact lens to better deliver the active ingredient and potentially with fewer side effects as the dosing is better controlled. It is known that drug delivery from a contact lens can result in several times higher bioavailability than eye drops due to the direct transfer of a drug to cornea across a thin tear layer. Using our dual layer contact lens platform and charged boundary layer technology we will resolve the deficiencies of current therapy by (1) Delivering cyclosporine at low concentration consistently for 8 hours/day using a drug eluting contact lens to allow a precise accumulation of cyclosporine on corneal surface, (2) Delivering cyclosporine loaded cationic nanocarriers from a novel drug eluting contact lens to improve the nanocarrier adhesion to cornea and conjunctiva surface and enhance cyclosporine penetration into the anterior chamber, (3) Conducting in vitro cell-based cytotoxicity studies of the nanocarriers and by means of an ex vivo porcine eye model measure cyclosporine corneal penetration efficacy of the drug eluting contact lens devices.