Cargando…

Investigation of the Cellular Effects of Beta- Cyclodextrin Derivatives on Caco-2 Intestinal Epithelial Cells

Cyclodextrins are widely used excipients for increasing water-solubility, delivery and bioavailability of lipophilic drugs. By using fluorescent cyclodextrin derivatives, we showed previously that cyclodextrins are able to enter Caco-2 intestinal cells by endocytosis, but the influence of different...

Descripción completa

Detalles Bibliográficos
Autores principales: Rusznyák, Ágnes, Malanga, Milo, Fenyvesi, Éva, Szente, Lajos, Váradi, Judit, Bácskay, Ildikó, Vecsernyés, Miklós, Vasvári, Gábor, Haimhoffer, Ádám, Fehér, Pálma, Ujhelyi, Zoltán, Nagy Jr., Béla, Fejes, Zsolt, Fenyvesi, Ferenc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911713/
https://www.ncbi.nlm.nih.gov/pubmed/33504045
http://dx.doi.org/10.3390/pharmaceutics13020157
_version_ 1783656406471147520
author Rusznyák, Ágnes
Malanga, Milo
Fenyvesi, Éva
Szente, Lajos
Váradi, Judit
Bácskay, Ildikó
Vecsernyés, Miklós
Vasvári, Gábor
Haimhoffer, Ádám
Fehér, Pálma
Ujhelyi, Zoltán
Nagy Jr., Béla
Fejes, Zsolt
Fenyvesi, Ferenc
author_facet Rusznyák, Ágnes
Malanga, Milo
Fenyvesi, Éva
Szente, Lajos
Váradi, Judit
Bácskay, Ildikó
Vecsernyés, Miklós
Vasvári, Gábor
Haimhoffer, Ádám
Fehér, Pálma
Ujhelyi, Zoltán
Nagy Jr., Béla
Fejes, Zsolt
Fenyvesi, Ferenc
author_sort Rusznyák, Ágnes
collection PubMed
description Cyclodextrins are widely used excipients for increasing water-solubility, delivery and bioavailability of lipophilic drugs. By using fluorescent cyclodextrin derivatives, we showed previously that cyclodextrins are able to enter Caco-2 intestinal cells by endocytosis, but the influence of different fluorescent labeling on the same cyclodextrin derivative has not been studied. The consequences of the cellular internalization of cyclodextrins have not been revealed yet either. The aims of this study were to compare the cellular internalization of fluorescein- and rhodamine-labeled (2-hydroxypropyl)-, (HPBCD) and randommethyl-β-cyclodextrins (RAMEB) and to investigate the intracellular effects of these derivatives on Caco-2 cells. Stimulation of the NF-kappa B pathway and autophagy and localization of these derivatives in lysosomes were tested. The endocytosis of these derivatives was examined by fluorescence microscopy and flow cytometry. Both fluorescein- and rhodamine-labeled derivatives entered the cells, therefore the type of the fluorescent labeling did not influence their internalization. Cyclodextrin pretreatment did not activate the translocation of the p65 subunit of the NF-kappa B heterodimer into the cell nuclei from the cytoplasm. After HPBCD or RAMEB treatment, formation of the autophagosomes did not increase compared to the control sample and at the same time these derivatives could be detected in lysosomes after internalization.
format Online
Article
Text
id pubmed-7911713
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-79117132021-02-28 Investigation of the Cellular Effects of Beta- Cyclodextrin Derivatives on Caco-2 Intestinal Epithelial Cells Rusznyák, Ágnes Malanga, Milo Fenyvesi, Éva Szente, Lajos Váradi, Judit Bácskay, Ildikó Vecsernyés, Miklós Vasvári, Gábor Haimhoffer, Ádám Fehér, Pálma Ujhelyi, Zoltán Nagy Jr., Béla Fejes, Zsolt Fenyvesi, Ferenc Pharmaceutics Article Cyclodextrins are widely used excipients for increasing water-solubility, delivery and bioavailability of lipophilic drugs. By using fluorescent cyclodextrin derivatives, we showed previously that cyclodextrins are able to enter Caco-2 intestinal cells by endocytosis, but the influence of different fluorescent labeling on the same cyclodextrin derivative has not been studied. The consequences of the cellular internalization of cyclodextrins have not been revealed yet either. The aims of this study were to compare the cellular internalization of fluorescein- and rhodamine-labeled (2-hydroxypropyl)-, (HPBCD) and randommethyl-β-cyclodextrins (RAMEB) and to investigate the intracellular effects of these derivatives on Caco-2 cells. Stimulation of the NF-kappa B pathway and autophagy and localization of these derivatives in lysosomes were tested. The endocytosis of these derivatives was examined by fluorescence microscopy and flow cytometry. Both fluorescein- and rhodamine-labeled derivatives entered the cells, therefore the type of the fluorescent labeling did not influence their internalization. Cyclodextrin pretreatment did not activate the translocation of the p65 subunit of the NF-kappa B heterodimer into the cell nuclei from the cytoplasm. After HPBCD or RAMEB treatment, formation of the autophagosomes did not increase compared to the control sample and at the same time these derivatives could be detected in lysosomes after internalization. MDPI 2021-01-25 /pmc/articles/PMC7911713/ /pubmed/33504045 http://dx.doi.org/10.3390/pharmaceutics13020157 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
Rusznyák, Ágnes
Malanga, Milo
Fenyvesi, Éva
Szente, Lajos
Váradi, Judit
Bácskay, Ildikó
Vecsernyés, Miklós
Vasvári, Gábor
Haimhoffer, Ádám
Fehér, Pálma
Ujhelyi, Zoltán
Nagy Jr., Béla
Fejes, Zsolt
Fenyvesi, Ferenc
Investigation of the Cellular Effects of Beta- Cyclodextrin Derivatives on Caco-2 Intestinal Epithelial Cells
title Investigation of the Cellular Effects of Beta- Cyclodextrin Derivatives on Caco-2 Intestinal Epithelial Cells
title_full Investigation of the Cellular Effects of Beta- Cyclodextrin Derivatives on Caco-2 Intestinal Epithelial Cells
title_fullStr Investigation of the Cellular Effects of Beta- Cyclodextrin Derivatives on Caco-2 Intestinal Epithelial Cells
title_full_unstemmed Investigation of the Cellular Effects of Beta- Cyclodextrin Derivatives on Caco-2 Intestinal Epithelial Cells
title_short Investigation of the Cellular Effects of Beta- Cyclodextrin Derivatives on Caco-2 Intestinal Epithelial Cells
title_sort investigation of the cellular effects of beta- cyclodextrin derivatives on caco-2 intestinal epithelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911713/
https://www.ncbi.nlm.nih.gov/pubmed/33504045
http://dx.doi.org/10.3390/pharmaceutics13020157
work_keys_str_mv AT rusznyakagnes investigationofthecellulareffectsofbetacyclodextrinderivativesoncaco2intestinalepithelialcells
AT malangamilo investigationofthecellulareffectsofbetacyclodextrinderivativesoncaco2intestinalepithelialcells
AT fenyvesieva investigationofthecellulareffectsofbetacyclodextrinderivativesoncaco2intestinalepithelialcells
AT szentelajos investigationofthecellulareffectsofbetacyclodextrinderivativesoncaco2intestinalepithelialcells
AT varadijudit investigationofthecellulareffectsofbetacyclodextrinderivativesoncaco2intestinalepithelialcells
AT bacskayildiko investigationofthecellulareffectsofbetacyclodextrinderivativesoncaco2intestinalepithelialcells
AT vecsernyesmiklos investigationofthecellulareffectsofbetacyclodextrinderivativesoncaco2intestinalepithelialcells
AT vasvarigabor investigationofthecellulareffectsofbetacyclodextrinderivativesoncaco2intestinalepithelialcells
AT haimhofferadam investigationofthecellulareffectsofbetacyclodextrinderivativesoncaco2intestinalepithelialcells
AT feherpalma investigationofthecellulareffectsofbetacyclodextrinderivativesoncaco2intestinalepithelialcells
AT ujhelyizoltan investigationofthecellulareffectsofbetacyclodextrinderivativesoncaco2intestinalepithelialcells
AT nagyjrbela investigationofthecellulareffectsofbetacyclodextrinderivativesoncaco2intestinalepithelialcells
AT fejeszsolt investigationofthecellulareffectsofbetacyclodextrinderivativesoncaco2intestinalepithelialcells
AT fenyvesiferenc investigationofthecellulareffectsofbetacyclodextrinderivativesoncaco2intestinalepithelialcells