International journal of molecular sciences, 2021-04, Vol.22 (9), p.4404
2021
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- Autor(en) / Beteiligte
- Titel
- Assessment of a New Nanostructured Microemulsion System for Ocular Delivery of Sorafenib to Posterior Segment of the Eye
- Ist Teil von
- International journal of molecular sciences, 2021-04, Vol.22 (9), p.4404
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms22094404Titel-ID: cdi_doaj_primary_oai_doaj_org_article_593cdf1fe0e64801a43c5888ecdbed9a
- Format
- –
- Schlagworte
- Administration, Ophthalmic, Angiogenesis, Animals, anti-VEGF, Choroidal Neovascularization - drug therapy, Cornea, Cytotoxicity, Diabetes, Diabetes mellitus, Diabetes Mellitus, Experimental - complications, Diabetic retinopathy, Diabetic Retinopathy - drug therapy, Diabetic Retinopathy - etiology, Diabetic Retinopathy - pathology, Disease Models, Animal, Drug therapy, Emulsions, Eye, Female, Growth factors, Inflammation, Insulin, Insulin-like growth factor I, Ischemia, Macular degeneration, Male, Mice, Mice, Inbred C57BL, Microemulsions, Mortality, Nanostructures - administration & dosage, Nanostructures - chemistry, NF-κB protein, Nitric oxide, Nitric-oxide synthase, ocular drug delivery system, Protein Kinase Inhibitors - administration & dosage, Protein Kinase Inhibitors - pharmacology, Rabbits, Rats, Rats, Sprague-Dawley, Reperfusion, Retina, Retinal Diseases - drug therapy, Retinal Diseases - pathology, Retinal Neovascularization - drug therapy, sorafenib, Sorafenib - administration & dosage, Sorafenib - pharmacology, Streptozocin, Targeted cancer therapy, Tumor necrosis factor-α, tyrosine kinase inhibitors, Vascular endothelial growth factor, Vascularization