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Cytotoxicity of β-Cyclodextrins in Retinal Explants for Intravitreal Drug Formulations

Cyclodextrins (CDs) have been widely used as pharmaceutical excipients for formulation purposes for different delivery systems. Recent studies have shown that CDs are able to form complexes with a variety of biomolecules, such as cholesterol. This has subsequently paved the way for the possibility o...

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Autores principales: Prajapati, Manisha, Christensen, Gustav, Paquet-Durand, François, Loftsson, Thorsteinn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967144/
https://www.ncbi.nlm.nih.gov/pubmed/33803405
http://dx.doi.org/10.3390/molecules26051492
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author Prajapati, Manisha
Christensen, Gustav
Paquet-Durand, François
Loftsson, Thorsteinn
author_facet Prajapati, Manisha
Christensen, Gustav
Paquet-Durand, François
Loftsson, Thorsteinn
author_sort Prajapati, Manisha
collection PubMed
description Cyclodextrins (CDs) have been widely used as pharmaceutical excipients for formulation purposes for different delivery systems. Recent studies have shown that CDs are able to form complexes with a variety of biomolecules, such as cholesterol. This has subsequently paved the way for the possibility of using CDs as drugs in certain retinal diseases, such as Stargardt disease and retinal artery occlusion, where CDs could absorb cholesterol lumps. However, studies on the retinal toxicity of CDs are limited. The purpose of this study was to examine the retinal toxicity of different beta-(β)CD derivatives and their localization within retinal tissues. To this end, we performed cytotoxicity studies with two different CDs—2-hydroxypropyl-βCD (HPβCD) and randomly methylated β-cyclodextrin (RMβCD)—using wild-type mouse retinal explants, the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and fluorescence microscopy. RMβCD was found to be more toxic to retinal explants when compared to HPβCD, which the retina can safely tolerate at levels as high as 10 mM. Additionally, studies conducted with fluorescent forms of the same CDs showed that both CDs can penetrate deep into the inner nuclear layer of the retina, with some uptake by Müller cells. These results suggest that HPβCD is a safer option than RMβCD for retinal drug delivery and may advance the use of CDs in the development of drugs designed for intravitreal administration.
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spelling pubmed-79671442021-03-18 Cytotoxicity of β-Cyclodextrins in Retinal Explants for Intravitreal Drug Formulations Prajapati, Manisha Christensen, Gustav Paquet-Durand, François Loftsson, Thorsteinn Molecules Article Cyclodextrins (CDs) have been widely used as pharmaceutical excipients for formulation purposes for different delivery systems. Recent studies have shown that CDs are able to form complexes with a variety of biomolecules, such as cholesterol. This has subsequently paved the way for the possibility of using CDs as drugs in certain retinal diseases, such as Stargardt disease and retinal artery occlusion, where CDs could absorb cholesterol lumps. However, studies on the retinal toxicity of CDs are limited. The purpose of this study was to examine the retinal toxicity of different beta-(β)CD derivatives and their localization within retinal tissues. To this end, we performed cytotoxicity studies with two different CDs—2-hydroxypropyl-βCD (HPβCD) and randomly methylated β-cyclodextrin (RMβCD)—using wild-type mouse retinal explants, the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and fluorescence microscopy. RMβCD was found to be more toxic to retinal explants when compared to HPβCD, which the retina can safely tolerate at levels as high as 10 mM. Additionally, studies conducted with fluorescent forms of the same CDs showed that both CDs can penetrate deep into the inner nuclear layer of the retina, with some uptake by Müller cells. These results suggest that HPβCD is a safer option than RMβCD for retinal drug delivery and may advance the use of CDs in the development of drugs designed for intravitreal administration. MDPI 2021-03-09 /pmc/articles/PMC7967144/ /pubmed/33803405 http://dx.doi.org/10.3390/molecules26051492 Text en © 2021 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 Article
Prajapati, Manisha
Christensen, Gustav
Paquet-Durand, François
Loftsson, Thorsteinn
Cytotoxicity of β-Cyclodextrins in Retinal Explants for Intravitreal Drug Formulations
title Cytotoxicity of β-Cyclodextrins in Retinal Explants for Intravitreal Drug Formulations
title_full Cytotoxicity of β-Cyclodextrins in Retinal Explants for Intravitreal Drug Formulations
title_fullStr Cytotoxicity of β-Cyclodextrins in Retinal Explants for Intravitreal Drug Formulations
title_full_unstemmed Cytotoxicity of β-Cyclodextrins in Retinal Explants for Intravitreal Drug Formulations
title_short Cytotoxicity of β-Cyclodextrins in Retinal Explants for Intravitreal Drug Formulations
title_sort cytotoxicity of β-cyclodextrins in retinal explants for intravitreal drug formulations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967144/
https://www.ncbi.nlm.nih.gov/pubmed/33803405
http://dx.doi.org/10.3390/molecules26051492
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