S.P. Barman, S. Harris, K. Barman and K. Ward
Symphony Therapeutics,
United States
Keywords: ophthalmic sun-block, eye-drop, OcuHeal
Summary:
UV exposure of ocular tissues has been linked to multiple disorders of the eye, some of which can lead to blindness (Turbert, 2020). These disorders are corneal pterygium (ocular surface growths), corneal blebs, corneal and scleral burns, cataract formation, corneal thinning, corneal ulcers, retinal burns, glaucoma and macular degeneration. The World Health Organization (WHO) has reported that corneal blindness is a critical cause of blindness worldwide where either loss of transparency or distortion of the refractive surface causes vision impairment (WHO, 2022). Chronic exposure to UV can cause damage to the anterior pole of the eye, ranging from minor (pterygium) to serious photokeratitis. In the veterinary markets, UV damage to ocular tissues can lead to corneal opacity, pannus, cataracts and ocular carcinoma. UV radiation from sunlight is categorized based on wavelength: UVA (315-400 nm), UVB (280-315 nm) and UVC (100-280 nm). More than 90% of UVB and 60% of UVA radiation is absorbed by the cornea, whereas the retina and deeper ocular tissues absorbed UV light in the range 300-800 nm, with the most phototoxic effect on the retina at wavelengths around ~430 nm (“blue light”). UV light that damages ocular tissues are primarily due to UVA and UVB (UVC is filtered out by the ozone layer), causing photochemical damage to cellular DNA due to the spontaneous production of reactive oxygen species. The production of reactive oxygen species elicits the production of pro-inflammatory species causing degeneration of critical ocular tissues. A clinical need exists for a pharmaceutically compliant ophthalmic product with UV-blocking properties and ideally, a product that can prevent and heal ocular tissue damage. We have developed OcuHeal-UV400+, a lipid nanoparticle eye-drop product that contains a flavonoid, found abundantly in fruit and vegetables. IB0108 is a small molecule of molecular weight < 500 Daltons, has FDA GRAS status as an oral supplement, has anti-oxidant capabilities, is biocompatible to the ocular surface and blocks portions of UVA and UVB. When incorporated/encapsulated into Symphony’s proprietary lipid nanoparticle technology (OcuHeal™), the entire UV light wavelength range from 200-550 nm are blocked, thus enhancing the properties of the UV-blocking molecule. Additionally, it’s potent anti-oxidant and anti-inflammatory properties renders a healing and protective effect to the ocular surface. We present data that demonstrates the UV-blocking properties of the product, distribution of the anti-oxidant throughout the eye and preclinical safety and tolerability. Manufacturing and sterilization processes have been developed to enable a sterile, ophthalmic product, stable at room temperature. OcuHeal-UV400+ sterile eye-drops are compliant to ophthalmic criteria with osmolality in the range 300-320 mOsm/L, a mean particle size in the range 70-100 nm, preservative-free and with viscosity in the range 60-100 centipoise. The utility of this product as a preventive and curative measure to UV damage on the ocular surface is extraordinary. Currently, there are no ophthalmic UV-protective medications in either the veterinary or human markets.