Noninvasive ocular delivery of adalimumab-loaded nanostructured lipid carriers for targeted retinitis pigmentosa therapy
Retinitis pigmentosa is a genetically heterogeneous retinal degeneration process. There is hardly any treatment available. It is associated with extensive chronic inflammation and the release of proinflammatory cytokines such as TNFα. The blockade of TNFα through systemic or intraocular routes slows...
| Autores: | , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad Católica de Valencia San Vicente Mártir |
| Repositorio: | RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir |
| Idioma: | inglés |
| OAI Identifier: | oai:riucv.ucv.es:20.500.12466/5782 |
| Acceso en línea: | http://hdl.handle.net/20.500.12466/5782 |
| Access Level: | acceso abierto |
| Palabra clave: | Retinitis pigmentosa Nanostructured lipid carriers Inflammation Eye drops Adalimumab Neuroprotection 32 Ciencias Médicas |
| Sumario: | Retinitis pigmentosa is a genetically heterogeneous retinal degeneration process. There is hardly any treatment available. It is associated with extensive chronic inflammation and the release of proinflammatory cytokines such as TNFα. The blockade of TNFα through systemic or intraocular routes slows retinal degeneration. They are invasive routes with possible side effects. Herein, we propose a noninvasive approach to address the inflammatory component of retinitis pigmentosa. This approach is based on the development of eye drops of nanostructured lipid carriers (NLCs) loaded with the monoclonal antibody against TNFα, adalimumab (ADA). We physicochemically characterized NLC–ADA. We evaluated retinal and corneal toxicity; corneal permeation; diffusion to the retina; and effects on retinal dysfunction, degeneration and inflammation. These results prove that NLC–ADA eye drops exhibit excellent corneal permeation, no toxicity and high retinal distribution in mice. These compounds improve retinal function, reduce retinal degeneration and ameliorate the inflammatory process. In particular, NLC–ADA eye drops reduce M1 microglial activation, macrophage infiltration and the levels of some components of the NLRP3 inflammasome in rd10 mice, a model of retinitis pigmentosa. This strategy offers a noninvasive route that circumvents the blood–retinal barrier in a safe and efficient manner. Hence, this approach could offer a promising therapeutic option for treating retinitis pigmentosa regardless of genetic defects. This approach could be useful for other inflammation-related retinal diseases. |
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