Eye drop formulations allowing topical treatment of retinal pathologies have long been sought as alternatives to intravitreal administration. This study aimed to assess whether a novel nanostructured microemulsions system (NaMESys) could be usefully employed to deliver sorafenib to the retina following topical instillation. NaMESys carrying 0.3% sorafenib (NaMESys‐SOR) proved to be cytocompatible in vitro on rabbit corneal cells, and well‐tolerated following b.i.d. ocular administration to rabbits during a 3‐month study. In rats subject to retinal ischemiareperfusion, NaMESys‐SOR significantly inhibited retinal expression of tumor necrosis factor‐alpha (TNFα, 20.7%) and inducible nitric oxide synthase (iNos, 87.3%) mRNAs in comparison to controls. Similarly, in streptozotocin‐induced diabetic rats, NaMESys‐SOR inhibited retinal expression of nuclear factor kappa B (NFκB), TNFα, insulin like growth factor 1 (IGF1), IGF1 receptor (IGF1R), vascular endothelial growth factor receptor 1 (VEGFR1) and 2 (VEGFR2) mRNAs by three‐fold on average compared to controls. Furthermore, a reduction in TNFα, VEGFR1 and VEGFR2 protein expression was observed by western blot. Moreover, in mice subject to laser‐induced choroidal neovascularization, NaMESys‐SOR significantly inhibited neovascular lesions by 54%. In conclusion, NaMESys‐SOR was shown to be a well‐tolerated ophthalmic formulation able to deliver effective amounts of sorafenib to the retina, reducing proinflammatory and pro‐angiogenic mediators in reliable models of proliferative retinopathies. These findings warrant further investigations on the full therapeutic potential of NaMESys‐SOR eye drops, aiming to address unmet needs in the pharmacotherapy of retinal neovascular diseases.

Assessment of a new nanostructured microemulsion system for ocular delivery of sorafenib to posterior segment of the eye

Platania C. B. M.;Maugeri G.;D'agata V.;Bucolo C.;
2021-01-01

Abstract

Eye drop formulations allowing topical treatment of retinal pathologies have long been sought as alternatives to intravitreal administration. This study aimed to assess whether a novel nanostructured microemulsions system (NaMESys) could be usefully employed to deliver sorafenib to the retina following topical instillation. NaMESys carrying 0.3% sorafenib (NaMESys‐SOR) proved to be cytocompatible in vitro on rabbit corneal cells, and well‐tolerated following b.i.d. ocular administration to rabbits during a 3‐month study. In rats subject to retinal ischemiareperfusion, NaMESys‐SOR significantly inhibited retinal expression of tumor necrosis factor‐alpha (TNFα, 20.7%) and inducible nitric oxide synthase (iNos, 87.3%) mRNAs in comparison to controls. Similarly, in streptozotocin‐induced diabetic rats, NaMESys‐SOR inhibited retinal expression of nuclear factor kappa B (NFκB), TNFα, insulin like growth factor 1 (IGF1), IGF1 receptor (IGF1R), vascular endothelial growth factor receptor 1 (VEGFR1) and 2 (VEGFR2) mRNAs by three‐fold on average compared to controls. Furthermore, a reduction in TNFα, VEGFR1 and VEGFR2 protein expression was observed by western blot. Moreover, in mice subject to laser‐induced choroidal neovascularization, NaMESys‐SOR significantly inhibited neovascular lesions by 54%. In conclusion, NaMESys‐SOR was shown to be a well‐tolerated ophthalmic formulation able to deliver effective amounts of sorafenib to the retina, reducing proinflammatory and pro‐angiogenic mediators in reliable models of proliferative retinopathies. These findings warrant further investigations on the full therapeutic potential of NaMESys‐SOR eye drops, aiming to address unmet needs in the pharmacotherapy of retinal neovascular diseases.
Angiogenesis
Anti‐VEGF
Eye drops
Ocular drug delivery system
Retina
Sorafenib
Tyrosine kinase inhibitors
Administration, Ophthalmic
Animals
Choroidal Neovascularization
Diabetes Mellitus, Experimental
Diabetic Retinopathy
Disease Models, Animal
Emulsions
Female
Male
Mice
Mice, Inbred C57BL
Nanostructures
Protein Kinase Inhibitors
Rabbits
Rats
Rats, Sprague-Dawley
Retinal Diseases
Retinal Neovascularization
Sorafenib
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/523929
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