ИСТИНА

Inflammatory eye diseases are the most prevalent eye pathologies which lead to partial disability and, sometimes, to the complete loss of vision. Among these diseases, the most severe one is uveitis, inflammation of uveal tract involving both outer and inner structures of the eye. The incidence of uveitis in the structure of common ocular pathology is 5-12%, this disease being responsible for 7–20% of blindness. One of the approaches to the treatment of inflammatory processes at uveitis is the use of antioxidants, in particular, superoxide dismutase1 (SOD1). However, only 5–10% of applied drug during topical instillations penetrates the cornea and reaches the intraocular tissues. In order to enhance the efficacy of enzyme penetration through the cornea barrier, SOD1 containing polymeric nanoparticles was prepared. As a result, nanoformulations based on complexes of recombinant human enzyme SOD1 with methoxy-poly(ethyleneglycol)-poly(L-lysine)50 block copolymer cross-linked by 3,3’-dithiobis(sulfosuccinimidyl propionate), as well as nanoformulations based on double layer complexes of SOD1 with protamine and block copolymer of methoxy-poly(ethylene glycol)-block-poly(L-glutamic acid sodium salt) cross-linked with glutaraldehyde were obtained. In an experimental model of immunogenic uveitis in rabbits, the biochemical indicators of the disease were significantly improved during topical instillations of the solution of a recombinant SOD1 incorporated into polymeric nanoparticles compared to the same treatment by an aqueous solution of the enzyme or placebo. Significant reduction of the duration of corneal and eyelid edema, decrease in the amount of fibrin clots, mitigation of lens opacity, as well as mitigation of conjunctival hyperemia, increase in antioxidant activity in the lacrimal fluid, and decrease in leukocyte count, the total protein and α2-macroglobulin activity in the aqueous humor of rabbits were observed. The data have been confirmed by histological studies of various eye tissues. The results obtained demonstrate the potential of nanoformulations based on SOD1 as promising therapeutic agents for ophthalmology.