Abstract
Purpose :
Dry eye disease (DED) is a chronic condition affecting over 16.4 million Americans, though the market leading product, Restasis, requires twice a day dosing and clinical efficacy can take 6 months to manifest. We have developed an eye drop containing mucoadhesive micelles which allow for greater drug loading and reduced dosing frequency compared to Restasis. Here we demonstrate the efficacy of these micelles in a diseased animal model and show the pharmacokinetic profile of the drug in the tissues.
Methods :
Polymeric micelles containing Cyclosporine A (CycA), the active drug in Restasis, were used in a scopolamine-induced dry eye disease (DED) model in Norway Brown rats to compare the effectiveness of the polymer formulation with Restasis. New Zealand White Rabbits were used for a 15 day pharmacokinetic study comparing the CycA micelle formulation, Restasis and unloaded micelles. Ocular tissues, including aqueous humour, and blood were harvested, homogenized and extracted to determine respective CycA levels via liquid chromatography-mass spectrometry (LC-MS).
Results :
In the rat dry eye model, both Restasis and the CycA-loaded micelles administered twice a day resolved dry eye symptoms as measured by tear volume and fluorescein staining, as shown in the figure. When dosing was extended to once every three days, Restasis drops did not resolve symptoms but the CycA micelles were able to resolve the condition by both metrics, indicating the prolonged action of the micelle formulation. Some resolution of symptoms were also seen with micelles dosed every 5 days.
Conclusions :
These polymeric micelles, formulated as an eye drop, offer an improved treatment option for dry eye disease. They demonstrate similar efficacy and therapeutic dosages relative to the market leader, Restasis, but with a substantially reduced dosage frequency. In rat and rabbit models, similar results have been achieved using the CycA loaded micelles every three days as Restasis dosed twice daily, demonstrating the prolong effect of the micelles. This polymeric formulation could be used with other therapeutic agents to develop longer-acting eye drop treatments for other ocular conditions in the future beyond just CycA for dry eye disease.
This is a 2020 ARVO Annual Meeting abstract.