(489q) Delivery of Cyclosporin A by Puncta Plugs for the Treatment of Dry Eyes

Currently 30 million people in US suffer from dry eyes. A common treatment for dry eyes includes blockage of tear drainage from the eyes to the nose by insertion of a plug in the duct that connects the eyes to the nose. Also, delivery of Restasis, which is a castor oil emulsion containing a drug cyclosporin A is a prescribed treatment for treating dry eyes. The residence time and bioavailability of cyclosporin delivered as Restasis is relatively small due to tear drainage. We propose to combine the two treatment modalities into one by developing a puncta plug that can release cyclosporin A for extended periods of time at therapeutic dose.

Our design for puncta plugs includes a cyclosporin A containing HEMA (Hydroxy Ethyl Methacrylate) core, with a fraction of the length coated by a silicon shell. These plugs have a core diameter of 0.53 mm and a plug diameter of 0.93mm, have an exposed length of 2mm and an overall length of 3mm. The plugs will be inserted with the coated side towards the nose so that drug can diffuse radially outwards from the uncoated section and then diffuse axially through the tears into the eyes. The ratio of exposed to unexposed length can be adjusted to suit the therapeutic requirement.

Plugs have been successfully prepared that have a zero order release of cyclosporin A for a period of 40 days at a rate of about 4 µg/day. Several in vitro experiments have been conducted to study the effect of drug concentration in the core, effect of crosslinking in the core and the effect of ratio of exposed to unexposed part on drug release. Also, the plugs do not have any initial burst of drug; therefore there would be no problem of over dosage while using these plugs.

Puncta plugs are made of bio-compatible materials and can release cyclosporin A for a period of more than 40 days at a therapeutic rate. The rate of release can be controlled by varying the crosslinking or the drug loading in the core. The plugs developed can also be used to deliver different drugs for other diseases apart from dry eyes.