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...

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Authors: Velasco, Sheyla, Gallego, Idoia, Olivares González, Lorena, Puras, Gustavo, Castro, María Carmen, Salom Alonso, David, Pedraz, José Luis, Rodrigo Nicolás, Regina
Format: article
Publication Date:2025
Country:España
Institution:Universidad Católica de Valencia San Vicente Mártir
Repository:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
Language:English
OAI Identifier:oai:riucv.ucv.es:20.500.12466/5782
Online Access:http://hdl.handle.net/20.500.12466/5782
Access Level:Open access
Keyword:Retinitis pigmentosa
Nanostructured lipid carriers
Inflammation
Eye drops
Adalimumab
Neuroprotection
32 Ciencias Médicas
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spelling Noninvasive ocular delivery of adalimumab-loaded nanostructured lipid carriers for targeted retinitis pigmentosa therapyVelasco, SheylaGallego, IdoiaOlivares González, LorenaPuras, GustavoCastro, María CarmenSalom Alonso, DavidPedraz, José LuisRodrigo Nicolás, ReginaRetinitis pigmentosaNanostructured lipid carriersInflammationEye dropsAdalimumabNeuroprotection32 Ciencias MédicasRetinitis 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.20252025-06-1220252025-04-0120252025-04-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12466/5782reponame:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártirinstname:Universidad Católica de Valencia San Vicente MártirInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:riucv.ucv.es:20.500.12466/57822026-06-19T08:32:07Z
dc.title.none.fl_str_mv Noninvasive ocular delivery of adalimumab-loaded nanostructured lipid carriers for targeted retinitis pigmentosa therapy
title Noninvasive ocular delivery of adalimumab-loaded nanostructured lipid carriers for targeted retinitis pigmentosa therapy
spellingShingle Noninvasive ocular delivery of adalimumab-loaded nanostructured lipid carriers for targeted retinitis pigmentosa therapy
Velasco, Sheyla
Retinitis pigmentosa
Nanostructured lipid carriers
Inflammation
Eye drops
Adalimumab
Neuroprotection
32 Ciencias Médicas
title_short Noninvasive ocular delivery of adalimumab-loaded nanostructured lipid carriers for targeted retinitis pigmentosa therapy
title_full Noninvasive ocular delivery of adalimumab-loaded nanostructured lipid carriers for targeted retinitis pigmentosa therapy
title_fullStr Noninvasive ocular delivery of adalimumab-loaded nanostructured lipid carriers for targeted retinitis pigmentosa therapy
title_full_unstemmed Noninvasive ocular delivery of adalimumab-loaded nanostructured lipid carriers for targeted retinitis pigmentosa therapy
title_sort Noninvasive ocular delivery of adalimumab-loaded nanostructured lipid carriers for targeted retinitis pigmentosa therapy
dc.creator.none.fl_str_mv Velasco, Sheyla
Gallego, Idoia
Olivares González, Lorena
Puras, Gustavo
Castro, María Carmen
Salom Alonso, David
Pedraz, José Luis
Rodrigo Nicolás, Regina
author Velasco, Sheyla
author_facet Velasco, Sheyla
Gallego, Idoia
Olivares González, Lorena
Puras, Gustavo
Castro, María Carmen
Salom Alonso, David
Pedraz, José Luis
Rodrigo Nicolás, Regina
author_role author
author2 Gallego, Idoia
Olivares González, Lorena
Puras, Gustavo
Castro, María Carmen
Salom Alonso, David
Pedraz, José Luis
Rodrigo Nicolás, Regina
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Retinitis pigmentosa
Nanostructured lipid carriers
Inflammation
Eye drops
Adalimumab
Neuroprotection
32 Ciencias Médicas
topic Retinitis pigmentosa
Nanostructured lipid carriers
Inflammation
Eye drops
Adalimumab
Neuroprotection
32 Ciencias Médicas
description 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.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-06-12
2025
2025-04-01
2025
2025-04-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12466/5782
url http://hdl.handle.net/20.500.12466/5782
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
instname:Universidad Católica de Valencia San Vicente Mártir
instname_str Universidad Católica de Valencia San Vicente Mártir
reponame_str RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
collection RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
repository.name.fl_str_mv
repository.mail.fl_str_mv
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