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R. A. Wassel, D. Chen, D. J. Nuno, A. B. Quiambao, J. L. Chodnicki, P. Margaron, J.-X. Ma, R. Farjo; Topical Ophthalmic Emulsion for Treatment of Retinal Vasculopathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2446.
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CLT-003, a novel small molecule, has been shown to inhibit angiogenesis and vascular leakage when injected into the vitreous humor. The purpose of this study was to develop an eye drop that can deliver therapeutic drug concentrations to the retina.
Three different emulsions were prepared ED-001, ED-002, and ED-003. There formulations were made up of oils and surfactants that are commonly used in ophthalmic formulations. Eyedrops (one drop of 40 µL/eye) were administered 4x per day for 6 days to Sprague Dawley rats. Gross clinical observation was conducted before each dosing. Standard ocular examinations to examine the anterior segment and ocular irritation were performed by an ophthalmologist using indirect ophthalmoscope and slit-lamp at least once day. Eyes were scored for chemosis, hyperemia, and swelling using a modified Hackett-McDonald system. Sprague Dawley rats were dosed for 6 days QID (one drop of 40 µL/eye) and then dissected retina and vitreous were taken for LC-MS/MS quantification of CLT-003.
Following topical QID administration of 1% CLT-003 in ED-001, ED-002, and ED-003 vehicles, it was observed that all three formulations tested were well tolerated, as assessed by ophthalmic examination. In the retina two of the formulations delivered 500 ng/g of drug and one formulation delivered 3 ug/g of drug. CLT-003 was also found in the vitreous as well.
CLT-003 emulsion eyedrops have demonstrated the ability to deliver the drug to the retina and vitreous over a 6 day period. These levels are significantly higher than we observed with intravitreal delivery of 1 or 5 µg CLT-003 in DMSO (at 2 days post-injection. The results suggest that CLT-003 topical ophthalmic emulsion may be a suitable therapeutic option for patients with retinal vasculopathies.
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