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Nanogel-Facilitated In-Situ Delivery of a Cataract Inhibitor

Cataracts are a leading cause of blindness worldwide. Surgical removal of cataracts is a safe and effective procedure to restore vision. However, a large number of patients later develop vision loss due to regrowth of lens cells and subsequent degradation of the visual axis leading to visual disabil...

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Autores principales: Gautam, Dixa, Pedler, Michelle G., Nair, Devatha P., Petrash, Jonathan Mark
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391309/
https://www.ncbi.nlm.nih.gov/pubmed/34439816
http://dx.doi.org/10.3390/biom11081150
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author Gautam, Dixa
Pedler, Michelle G.
Nair, Devatha P.
Petrash, Jonathan Mark
author_facet Gautam, Dixa
Pedler, Michelle G.
Nair, Devatha P.
Petrash, Jonathan Mark
author_sort Gautam, Dixa
collection PubMed
description Cataracts are a leading cause of blindness worldwide. Surgical removal of cataracts is a safe and effective procedure to restore vision. However, a large number of patients later develop vision loss due to regrowth of lens cells and subsequent degradation of the visual axis leading to visual disability. This postsurgical complication, known as posterior capsular opacification (PCO), occurs in up to 30% of cataract patients and has no clinically proven pharmacological means of prevention. Despite the availability of many compounds capable of preventing early steps in PCO development, there is currently no effective means to deliver such therapies into the eye for a suitable duration. To model a solution to this unmet medical need, we fabricated acrylic substrates as intraocular lens (IOL) mimics scaled to place into the capsular bag of the mouse lens following a mock-cataract surgery. Substrates were coated with a hydrophilic crosslinked acrylate nanogel designed to elute Sorbinil, an aldose reductase inhibitor previously shown to suppress PCO. Insertion of the Sorbinil-eluting device into the lens capsule at the time of cataract surgery resulted in substantial prevention of cellular changes associated with PCO development. This model demonstrates that a cataract inhibitor can be delivered into the postsurgical lens capsule at therapeutic levels.
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spelling pubmed-83913092021-08-28 Nanogel-Facilitated In-Situ Delivery of a Cataract Inhibitor Gautam, Dixa Pedler, Michelle G. Nair, Devatha P. Petrash, Jonathan Mark Biomolecules Article Cataracts are a leading cause of blindness worldwide. Surgical removal of cataracts is a safe and effective procedure to restore vision. However, a large number of patients later develop vision loss due to regrowth of lens cells and subsequent degradation of the visual axis leading to visual disability. This postsurgical complication, known as posterior capsular opacification (PCO), occurs in up to 30% of cataract patients and has no clinically proven pharmacological means of prevention. Despite the availability of many compounds capable of preventing early steps in PCO development, there is currently no effective means to deliver such therapies into the eye for a suitable duration. To model a solution to this unmet medical need, we fabricated acrylic substrates as intraocular lens (IOL) mimics scaled to place into the capsular bag of the mouse lens following a mock-cataract surgery. Substrates were coated with a hydrophilic crosslinked acrylate nanogel designed to elute Sorbinil, an aldose reductase inhibitor previously shown to suppress PCO. Insertion of the Sorbinil-eluting device into the lens capsule at the time of cataract surgery resulted in substantial prevention of cellular changes associated with PCO development. This model demonstrates that a cataract inhibitor can be delivered into the postsurgical lens capsule at therapeutic levels. MDPI 2021-08-04 /pmc/articles/PMC8391309/ /pubmed/34439816 http://dx.doi.org/10.3390/biom11081150 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gautam, Dixa
Pedler, Michelle G.
Nair, Devatha P.
Petrash, Jonathan Mark
Nanogel-Facilitated In-Situ Delivery of a Cataract Inhibitor
title Nanogel-Facilitated In-Situ Delivery of a Cataract Inhibitor
title_full Nanogel-Facilitated In-Situ Delivery of a Cataract Inhibitor
title_fullStr Nanogel-Facilitated In-Situ Delivery of a Cataract Inhibitor
title_full_unstemmed Nanogel-Facilitated In-Situ Delivery of a Cataract Inhibitor
title_short Nanogel-Facilitated In-Situ Delivery of a Cataract Inhibitor
title_sort nanogel-facilitated in-situ delivery of a cataract inhibitor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391309/
https://www.ncbi.nlm.nih.gov/pubmed/34439816
http://dx.doi.org/10.3390/biom11081150
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