MiDROPS™ for Topical Delivery of Lipophilic Compounds to the Anterior and Posterior Segment of the Eye

Abstract

Purpose : The topical delivery of lipophilic agents into the eye is a useful and effective treatment strategy for numerous forms of ophthalmic disease. We sought to construct and examine a library of microemulsions that can formulate and deliver lipophilic small molecules into both the anterior segment and posterior segment following topical instillation.

Methods : Utilizing oils and surfactants that are Generally Regarded As Safe (GRAS) and already utilized in FDA-approved ophthalmic pharmaceuticals, we conducted a high throughput screen of over 30,000 formulations to identify those which spontaneously self-assembled into microemulsions. This screening yielded a number of formulations (MiDROPS™) which are currently represented in a parent library of 672 microemulsions. Several small molecule agents with physiochemical properties of LogP values between 0.5 to 8 and molecular weights between 200 to 500 grams/mole have been successfully formulated in MiDROPS™. These formulations were evaluated for ocular tolerance and tissue distribution in numerous exaggerated dosing studies ranging from 5-30 days in mice, rats, and rabbits. These included detailed clinical ophthalmic examination, full necropsy, histopathology, and LC-MS quantification of the test agent in various tissues of the eye.

Results : We have successfully formulated numerous lipophilic test agents in MiDROPS™ which could deliver therapeutic levels of various drugs into the anterior and posterior segments of the eye in mice, rats, and rabbits. Higher levels of drug were present in the ocular tissues vs the aqueous and vitreous humor. Only a few formulations exhibited minor findings of ocular intolerability, and many formulations did not elicit any observable adverse effect at all.

Conclusions : We appear to be learning something fundamentally new as to how lipophilic test agents can access the eye after topical instillation and how certain surfactants can be well tolerated in high doses when formulated in the MiDROPS™ system. In addition to the ability to formulate difficult insoluble small molecules, MiDROPS™ are more stable than traditional emulsions due to their thermodynamic properties. Future clinical studies are planned to further evaluate the promise of this innovative technology for delivering new therapeutics into the eye for diseases of the posterior and anterior segment.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.