Topical nanoemulsion of a RUNX1 inhibitor for the treatment of pathologic ocular angiogenesis.

Abstract

Purpose

To test the efficacy of RUNX1 inhibition with topical nanoemulsion containing Ro5-3335 (eNano-Ro5) in experimental ocular neovascularization.

Design

Preclinical experimental study.

Participants

In vitro primary culture human retinal endothelial cell (HRECs) culture. C57BL/6J 6-10 week-old male and female mice.

Methods

We evaluated the effect of eNano-Ro5 in cell proliferation, cell toxicity and migration of HRECs. We used an alkali burn model of corneal neovascularization and a laser-induced model of choroidal neovascularization to test in vivo efficacy of eNano-Ro5 in pathologic angiogenesis in mice. We used mass spectrometry to measure penetration of Ro5-3335 released from the nanoemulsion in ocular tissues.

Main outcome measures

Neovascular area.

Results

RUNX1 inhibition reduced cell proliferation and migration in vitro. Mass spectrometry analysis revealed detectable levels of the active RUNX1 small molecule inhibitor Ro5-3335 in the anterior and posterior segment of the mice eyes. Topical treatment with eNano-Ro5 significantly reduced corneal neovascularization and improved corneal wound healing after alkali burn. Choroidal neovascularization lesion size and leakage were significantly reduced after treatment with topical eNano-Ro5.

Conclusions

Topical treatment with eNano-Ro5 is an effective and viable platform to deliver a small molecule RUNX1 inhibitor. This route of administration offers advantages that could improve the management and outcomes of these sight-threatening conditions. Topical non-invasive delivery of RUNX1 inhibitor could be beneficial for many patients suffering from pathological ocular neovascularization.