Harnessing cyclodextrins for enhanced ocular delivery of carotenoid derivatives: From development to ex vivo characterization

Lutein and zeaxanthin, prominent carotenoids with antioxidant properties, contribute notably to maintaining of ocular health. These substances reduce the harmful effect of oxidative stress and blue light and ensure the vision quality. Carotenoids-rich dietary could have ophthalmic benefits, such as...

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Main Authors: Réka Angi, Attila János Kalóczkai, Anna Kovács, András Marton, Vivien Bárdos, Péter Dormán, Gábor Katona, Attila Agócs, Anita Csorba, Zoltán Zs. Nagy, Anna Vincze, György T. Balogh
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Carbohydrate Polymer Technologies and Applications
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Online Access:http://www.sciencedirect.com/science/article/pii/S266689392500057X
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author Réka Angi
Attila János Kalóczkai
Anna Kovács
András Marton
Vivien Bárdos
Péter Dormán
Gábor Katona
Attila Agócs
Anita Csorba
Zoltán Zs. Nagy
Anna Vincze
György T. Balogh
author_facet Réka Angi
Attila János Kalóczkai
Anna Kovács
András Marton
Vivien Bárdos
Péter Dormán
Gábor Katona
Attila Agócs
Anita Csorba
Zoltán Zs. Nagy
Anna Vincze
György T. Balogh
author_sort Réka Angi
collection DOAJ
description Lutein and zeaxanthin, prominent carotenoids with antioxidant properties, contribute notably to maintaining of ocular health. These substances reduce the harmful effect of oxidative stress and blue light and ensure the vision quality. Carotenoids-rich dietary could have ophthalmic benefits, such as enhanced contrast perception and reduced eye fatigue, while also show potential in mitigating the risk of age-related macular degeneration (AMD). Nonetheless, ocular administration of carotenoids could enhance the local ophthalmic bioavailability of these compounds. The aim of this study was to investigate ophthalmic applicability of lutein (LutD) and zeaxanthin disuccinates (ZeaD) in aqueous solutions applying cyclodextrins to improve their solubility and permeability. Among the tested cyclodextrins, randomly methylated beta-cyclodextrin (RAMEB) was identified as the most effective solubilizing agent, achieving solubility values of 572±55 μM and 1470±103 μM for LutD and ZeaD, respectively. In vitro corneal-PAMPA and ex vivo porcine eye models demonstrated that RAMEB-based formulations significantly improved the permeability of both carotenoid derivatives by increasing their solubility (corneal concentration at 15 mins), markedly surpassing those of the reference suspensions. The findings suggest that RAMEB may be essential for developing carotenoid-based aqueous eye drops, leveraging its antioxidant properties to improve ocular health and ameliorate various degenerative eye conditions.
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spelling doaj-art-2522416c78a442fd93116ee78b7cd9702025-08-20T02:52:21ZengElsevierCarbohydrate Polymer Technologies and Applications2666-89392025-03-01910071810.1016/j.carpta.2025.100718Harnessing cyclodextrins for enhanced ocular delivery of carotenoid derivatives: From development to ex vivo characterizationRéka Angi0Attila János Kalóczkai1Anna Kovács2András Marton3Vivien Bárdos4Péter Dormán5Gábor Katona6Attila Agócs7Anita Csorba8Zoltán Zs. Nagy9Anna Vincze10György T. Balogh11Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre u. 9., H-1092 Budapest, Hungary; Center for Pharmacology and Drug Research & Development, Semmelweis University, Üllői u. 26. H-1092 Budapest, HungaryDepartment of Chemical and Process Engineering, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem Quay 3., H-1111 Budapest, HungaryDepartment of Chemical and Process Engineering, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem Quay 3., H-1111 Budapest, HungaryDepartment of Chemical and Process Engineering, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem Quay 3., H-1111 Budapest, HungaryDepartment of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre u. 9., H-1092 Budapest, Hungary; Center for Pharmacology and Drug Research & Development, Semmelweis University, Üllői u. 26. H-1092 Budapest, HungaryCenter for Pharmacology and Drug Research & Development, Semmelweis University, Üllői u. 26. H-1092 Budapest, Hungary; Department of Ophthalmology, Semmelweis University, Maria Str. 39., H-1085 Budapest, HungaryInstitute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös utca 6., H-6720 Szeged, HungaryDepartment of Biochemistry and Medical Chemistry, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, HungaryCenter for Pharmacology and Drug Research & Development, Semmelweis University, Üllői u. 26. H-1092 Budapest, Hungary; Department of Ophthalmology, Semmelweis University, Maria Str. 39., H-1085 Budapest, HungaryCenter for Pharmacology and Drug Research & Development, Semmelweis University, Üllői u. 26. H-1092 Budapest, Hungary; Department of Ophthalmology, Semmelweis University, Maria Str. 39., H-1085 Budapest, HungaryDepartment of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre u. 9., H-1092 Budapest, Hungary; Center for Pharmacology and Drug Research & Development, Semmelweis University, Üllői u. 26. H-1092 Budapest, Hungary; Corresponding authors.Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre u. 9., H-1092 Budapest, Hungary; Center for Pharmacology and Drug Research & Development, Semmelweis University, Üllői u. 26. H-1092 Budapest, Hungary; Department of Chemical and Process Engineering, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem Quay 3., H-1111 Budapest, Hungary; Corresponding authors.Lutein and zeaxanthin, prominent carotenoids with antioxidant properties, contribute notably to maintaining of ocular health. These substances reduce the harmful effect of oxidative stress and blue light and ensure the vision quality. Carotenoids-rich dietary could have ophthalmic benefits, such as enhanced contrast perception and reduced eye fatigue, while also show potential in mitigating the risk of age-related macular degeneration (AMD). Nonetheless, ocular administration of carotenoids could enhance the local ophthalmic bioavailability of these compounds. The aim of this study was to investigate ophthalmic applicability of lutein (LutD) and zeaxanthin disuccinates (ZeaD) in aqueous solutions applying cyclodextrins to improve their solubility and permeability. Among the tested cyclodextrins, randomly methylated beta-cyclodextrin (RAMEB) was identified as the most effective solubilizing agent, achieving solubility values of 572±55 μM and 1470±103 μM for LutD and ZeaD, respectively. In vitro corneal-PAMPA and ex vivo porcine eye models demonstrated that RAMEB-based formulations significantly improved the permeability of both carotenoid derivatives by increasing their solubility (corneal concentration at 15 mins), markedly surpassing those of the reference suspensions. The findings suggest that RAMEB may be essential for developing carotenoid-based aqueous eye drops, leveraging its antioxidant properties to improve ocular health and ameliorate various degenerative eye conditions.http://www.sciencedirect.com/science/article/pii/S266689392500057XLuteinZeaxanthinCyclodextrinsSolubilityCorneal permeabilityEx vivo
spellingShingle Réka Angi
Attila János Kalóczkai
Anna Kovács
András Marton
Vivien Bárdos
Péter Dormán
Gábor Katona
Attila Agócs
Anita Csorba
Zoltán Zs. Nagy
Anna Vincze
György T. Balogh
Harnessing cyclodextrins for enhanced ocular delivery of carotenoid derivatives: From development to ex vivo characterization
Carbohydrate Polymer Technologies and Applications
Lutein
Zeaxanthin
Cyclodextrins
Solubility
Corneal permeability
Ex vivo
title Harnessing cyclodextrins for enhanced ocular delivery of carotenoid derivatives: From development to ex vivo characterization
title_full Harnessing cyclodextrins for enhanced ocular delivery of carotenoid derivatives: From development to ex vivo characterization
title_fullStr Harnessing cyclodextrins for enhanced ocular delivery of carotenoid derivatives: From development to ex vivo characterization
title_full_unstemmed Harnessing cyclodextrins for enhanced ocular delivery of carotenoid derivatives: From development to ex vivo characterization
title_short Harnessing cyclodextrins for enhanced ocular delivery of carotenoid derivatives: From development to ex vivo characterization
title_sort harnessing cyclodextrins for enhanced ocular delivery of carotenoid derivatives from development to ex vivo characterization
topic Lutein
Zeaxanthin
Cyclodextrins
Solubility
Corneal permeability
Ex vivo
url http://www.sciencedirect.com/science/article/pii/S266689392500057X
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