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

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. In this Phase II project, we propose continuing the successful development of a drug delivery contact lens (DDCL) designed to manage dry eye by incorporating cyclosporine A (CsA) to better deliver the active ingredient with fewer side effects due to better control of dosing. An important discovery in Phase I was the use of hyaluronic acid (HA) improving CsA uptake and retention, with the potential for faster relief of symptoms due to HA's own lubricating and regenerative properties as a naturally occurring substance in the body. With the key aims of Phase I substantially completed, Phase II will focus on optimizing the DDCL with CsA and HA using active ingredients sourced from commercial manufacturers, and lenses with FDA 510(k) clearance for which we have rights to commercial use. The product can then be easily integrated into an existing contact lens production process for use in clinical trials following the project. Successful completion of the Phase II research strategy will include positive results by in vivo study and an IND application for clinical study of the DDCL in a human population. For the commercialization strategy, we have agreement with a global contact lens company to manufacture and supply the DDCL, and are negotiating a licensing agreement with this partner for selected regions. Investment and future royalties from the partner will allow our independent development of the DDCL for other markets in the future.