Endocytosis of fluorescent cyclodextrins by intestinal Caco-2 cells and its role in paclitaxel drug delivery.
Cyclodextrins are widely used excipients in pharmaceutical formulations. They are mainly utilized as solubilizers and absorption enhancers, but recent results revealed their effects on cell membranes and pharmacological barriers. In addition to the growing knowledge on their interaction with plasma membranes, it was confirmed that cyclodextrins are able to enter cells by endocytosis. The number of the tested cyclodextrins was limited, and the role of this mechanism in drug absorption and delivery is not known. Our aim was to examine the endocytosis of fluorescently labeled hydroxypropyl-β-cyclodextrin, random methyl-β-cyclodextrin and soluble β-cyclodextrin polymer, and the cellular uptake of the fluorescent paclitaxel derivative-random methyl-β-cyclodextrin complex. The studied cyclodextrin derivatives were able to enter Caco-2 intestinal cells and localized in vesicles in the cytoplasm, while their permeability was very limited through Caco-2 monolayers. We demonstrated for the first time that the fluorescent paclitaxel derivative and rhodamine-labeled random methyl-β-cyclodextrin were detected in the same intracellular vesicles after treating cells with their inclusion complex. These results indicate that the endocytosis of cyclodextrin complexes can contribute to drug absorption processes.
Department of Pharmaceutical Technology, University of Debrecen, H-4010 Nagyerdei St. 98, Debrecen, Hungary.
Katalin
K
Réti-Nagy
Cyclolab Cyclodextrin R&D Laboratory Ltd., H-1097 Illatos St. 7., Budapest, Hungary.
Milo
M
Malanga
Cyclolab Cyclodextrin R&D Laboratory Ltd., H-1097 Illatos St. 7., Budapest, Hungary.
Éva
É
Fenyvesi
Cyclolab Cyclodextrin R&D Laboratory Ltd., H-1097 Illatos St. 7., Budapest, Hungary.
Lajos
L
Szente
Department of Biophysics and Cell Biology, University of Debrecen, H-4010 Egyetem Sq. 1., Debrecen, Hungary.
György
G
Vámosi
Department of Pharmaceutical Technology, University of Debrecen, H-4010 Nagyerdei St. 98, Debrecen, Hungary.
Judit
J
Váradi
Department of Pharmaceutical Technology, University of Debrecen, H-4010 Nagyerdei St. 98, Debrecen, Hungary.
Ildikó
I
Bácskay
Department of Pharmaceutical Technology, University of Debrecen, H-4010 Nagyerdei St. 98, Debrecen, Hungary.
Pálma
P
Fehér
Department of Pharmaceutical Technology, University of Debrecen, H-4010 Nagyerdei St. 98, Debrecen, Hungary.
Zoltán
Z
Ujhelyi
Department of Pharmaceutical Technology, University of Debrecen, H-4010 Nagyerdei St. 98, Debrecen, Hungary.
Eszter
E
Róka
Department of Pharmaceutical Technology, University of Debrecen, H-4010 Nagyerdei St. 98, Debrecen, Hungary.
Miklós
M
Vecsernyés
Gedeon Richter Plc., H-1103 Gyömrői út 19-21., Budapest, Hungary.
György
G
Balogh
Department of Pharmaceutical Technology, University of Debrecen, H-4010 Nagyerdei St. 98, Debrecen, Hungary.
Gábor
G
Vasvári
Department of Pharmaceutical Technology, University of Debrecen, H-4010 Nagyerdei St. 98, Debrecen, Hungary. Electronic address: fenyvesi.ferenc@pharm.unideb.hu.
Ferenc
F
Fenyvesi
D018938:Caco-2 Cells; D003505:Cyclodextrins / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D004705:Endocytosis; D005434:Flow Cytometry; D005453:Fluorescence; D006801:Humans; D018613:Microscopy, Confocal; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010539:Permeability
D003505:Cyclodextrins; D017239:Paclitaxel
(2-Hydroxypropyl)-β-cyclodextrin (PubChem CID: 44134771); Caco-2; Cyclodextrin; Endocytosis; Paclitaxel; Paclitaxel (PubChem CID: 36314); Random methyl-β-cyclodextrin (PubChem CID: 51051622)