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Article

Assessment of a New Nanostructured Microemulsion System for Ocular Delivery of Sorafenib to Posterior Segment of the Eye

1
Research, Preclinical Development and Patents, SIFI S.p.A., Lavinaio-Aci S. Antonio, 95025 Catania, Italy
2
Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”–CNR, 80131 Napoli, Italy
3
Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Murat Dogru
Int. J. Mol. Sci. 2021, 22(9), 4404; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094404
Received: 18 March 2021 / Revised: 16 April 2021 / Accepted: 21 April 2021 / Published: 22 April 2021
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 ischemia-reperfusion, 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. View Full-Text
Keywords: ocular drug delivery system; retina; angiogenesis; anti-VEGF; tyrosine kinase inhibitors; sorafenib; eye drops ocular drug delivery system; retina; angiogenesis; anti-VEGF; tyrosine kinase inhibitors; sorafenib; eye drops
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MDPI and ACS Style

Santonocito, M.; Zappulla, C.; Viola, S.; La Rosa, L.R.; Solfato, E.; Abbate, I.; Tarallo, V.; Apicella, I.; Platania, C.B.M.; Maugeri, G.; D’Agata, V.; Bucolo, C.; De Falco, S.; Mazzone, M.G.; Giuliano, F. Assessment of a New Nanostructured Microemulsion System for Ocular Delivery of Sorafenib to Posterior Segment of the Eye. Int. J. Mol. Sci. 2021, 22, 4404. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094404

AMA Style

Santonocito M, Zappulla C, Viola S, La Rosa LR, Solfato E, Abbate I, Tarallo V, Apicella I, Platania CBM, Maugeri G, D’Agata V, Bucolo C, De Falco S, Mazzone MG, Giuliano F. Assessment of a New Nanostructured Microemulsion System for Ocular Delivery of Sorafenib to Posterior Segment of the Eye. International Journal of Molecular Sciences. 2021; 22(9):4404. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094404

Chicago/Turabian Style

Santonocito, Manuela, Cristina Zappulla, Santa Viola, Luca R. La Rosa, Elena Solfato, Ilenia Abbate, Valeria Tarallo, Ivana Apicella, Chiara B.M. Platania, Grazia Maugeri, Velia D’Agata, Claudio Bucolo, Sandro De Falco, Maria G. Mazzone, and Francesco Giuliano. 2021. "Assessment of a New Nanostructured Microemulsion System for Ocular Delivery of Sorafenib to Posterior Segment of the Eye" International Journal of Molecular Sciences 22, no. 9: 4404. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094404

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