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Topical Ocular Delivery of TGF-β1 to the Back of the Eye: Implications in Age-Related Neurodegenerative Diseases

Dysregulation of the transforming growth factor-β1 (TGF-β1)/selected small mother against decapentaplegic (SMAD) pathway can be implicated in development of age-related macular degeneration (AMD), and the delivery of TGF-β1 could be beneficial for AMD. We developed a new ophthalmic formulation of TG...

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Autores principales: Platania, Chiara Bianca Maria, Fisichella, Vincenzo, Fidilio, Annamaria, Geraci, Federica, Lazzara, Francesca, Leggio, Gian Marco, Salomone, Salvatore, Drago, Filippo, Pignatello, Rosario, Caraci, Filippo, Bucolo, Claudio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666758/
https://www.ncbi.nlm.nih.gov/pubmed/28973964
http://dx.doi.org/10.3390/ijms18102076
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author Platania, Chiara Bianca Maria
Fisichella, Vincenzo
Fidilio, Annamaria
Geraci, Federica
Lazzara, Francesca
Leggio, Gian Marco
Salomone, Salvatore
Drago, Filippo
Pignatello, Rosario
Caraci, Filippo
Bucolo, Claudio
author_facet Platania, Chiara Bianca Maria
Fisichella, Vincenzo
Fidilio, Annamaria
Geraci, Federica
Lazzara, Francesca
Leggio, Gian Marco
Salomone, Salvatore
Drago, Filippo
Pignatello, Rosario
Caraci, Filippo
Bucolo, Claudio
author_sort Platania, Chiara Bianca Maria
collection PubMed
description Dysregulation of the transforming growth factor-β1 (TGF-β1)/selected small mother against decapentaplegic (SMAD) pathway can be implicated in development of age-related macular degeneration (AMD), and the delivery of TGF-β1 could be beneficial for AMD. We developed a new ophthalmic formulation of TGF-β1 assessing the ocular pharmacokinetic profile of TGF-β1 in the rabbit eye. Small unilamellar vesicles (SUV) loaded with TGF-β1 were complemented with Annexin V and Ca(2+), and the vitreous bioavailability of TGF-β1 was assessed after topical ocular administration by a commercial ELISA kit. We detected high levels of TGF-β1 (C(max) 114.7 ± 12.40 pg/mL) in the vitreous after 60 min (T(max)) from the topical application of the liposomal suspension. Ocular tolerability was also assessed by a modified Draize’s test. The new formulation was well tolerated. In conclusion, we demonstrated that the novel formulation was able to deliver remarkable levels of TGF-β1 into the back of the eye after topical administration. Indeed, this TGF-β1 delivery system may be useful in clinical practice to manage ophthalmic conditions such as age-related macular degeneration, skipping invasive intraocular injections.
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spelling pubmed-56667582017-11-09 Topical Ocular Delivery of TGF-β1 to the Back of the Eye: Implications in Age-Related Neurodegenerative Diseases Platania, Chiara Bianca Maria Fisichella, Vincenzo Fidilio, Annamaria Geraci, Federica Lazzara, Francesca Leggio, Gian Marco Salomone, Salvatore Drago, Filippo Pignatello, Rosario Caraci, Filippo Bucolo, Claudio Int J Mol Sci Communication Dysregulation of the transforming growth factor-β1 (TGF-β1)/selected small mother against decapentaplegic (SMAD) pathway can be implicated in development of age-related macular degeneration (AMD), and the delivery of TGF-β1 could be beneficial for AMD. We developed a new ophthalmic formulation of TGF-β1 assessing the ocular pharmacokinetic profile of TGF-β1 in the rabbit eye. Small unilamellar vesicles (SUV) loaded with TGF-β1 were complemented with Annexin V and Ca(2+), and the vitreous bioavailability of TGF-β1 was assessed after topical ocular administration by a commercial ELISA kit. We detected high levels of TGF-β1 (C(max) 114.7 ± 12.40 pg/mL) in the vitreous after 60 min (T(max)) from the topical application of the liposomal suspension. Ocular tolerability was also assessed by a modified Draize’s test. The new formulation was well tolerated. In conclusion, we demonstrated that the novel formulation was able to deliver remarkable levels of TGF-β1 into the back of the eye after topical administration. Indeed, this TGF-β1 delivery system may be useful in clinical practice to manage ophthalmic conditions such as age-related macular degeneration, skipping invasive intraocular injections. MDPI 2017-09-30 /pmc/articles/PMC5666758/ /pubmed/28973964 http://dx.doi.org/10.3390/ijms18102076 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Platania, Chiara Bianca Maria
Fisichella, Vincenzo
Fidilio, Annamaria
Geraci, Federica
Lazzara, Francesca
Leggio, Gian Marco
Salomone, Salvatore
Drago, Filippo
Pignatello, Rosario
Caraci, Filippo
Bucolo, Claudio
Topical Ocular Delivery of TGF-β1 to the Back of the Eye: Implications in Age-Related Neurodegenerative Diseases
title Topical Ocular Delivery of TGF-β1 to the Back of the Eye: Implications in Age-Related Neurodegenerative Diseases
title_full Topical Ocular Delivery of TGF-β1 to the Back of the Eye: Implications in Age-Related Neurodegenerative Diseases
title_fullStr Topical Ocular Delivery of TGF-β1 to the Back of the Eye: Implications in Age-Related Neurodegenerative Diseases
title_full_unstemmed Topical Ocular Delivery of TGF-β1 to the Back of the Eye: Implications in Age-Related Neurodegenerative Diseases
title_short Topical Ocular Delivery of TGF-β1 to the Back of the Eye: Implications in Age-Related Neurodegenerative Diseases
title_sort topical ocular delivery of tgf-β1 to the back of the eye: implications in age-related neurodegenerative diseases
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666758/
https://www.ncbi.nlm.nih.gov/pubmed/28973964
http://dx.doi.org/10.3390/ijms18102076
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