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Open AccessArticle

Pharmacokinetic Properties of Fluorescently Labelled Hydroxypropyl-Beta-Cyclodextrin

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Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary
2
Department of Histology, Faculty of Medicine, ‘Vasile Goldiș’ Western University of Arad, 86 Rebreanu Street, 310414 Arad, Romania
3
Department of Biochemistry and Molecular Biology, University of Bucharest, Splaiul Independenței Street, no. 91–95, sector 5, 050095 Bucharest, Romania
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Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary
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MTA-DE Lendület Vascular Pathophysiology Research Group, Research Centre for Molecular Medicine, Faculty of Medicine, University of Debrecen, 4012 Debrecen, Hungary
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Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary
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Cyclolab Cyclodextrin R&D Laboratory Ltd., Illatos St. 7, H-1097 Budapest, Hungary
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University of Debrecen, Doctoral School of Pharmaceutical Sciences, Nagyerdei St. 98, H-4032 Debrecen, Hungary
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(10), 509; https://doi.org/10.3390/biom9100509
Received: 14 August 2019 / Revised: 9 September 2019 / Accepted: 15 September 2019 / Published: 20 September 2019
(This article belongs to the Special Issue Perspectives of Cyclodextrins)
2-Hydroxypropyl-beta-cyclodextrin (HPBCD) is utilized in the formulation of pharmaceutical products and recently orphan designation was granted for the treatment of Niemann–Pick disease, type C. The exact mechanism of HPBCD action and side effects are not completely explained. We used fluorescently labelled hydroxypropyl-beta-cyclodextrin (FITC-HPBCD) to study its pharmacokinetic parameters in mice and compare with native HPBCD data. We found that FITC-HPBCD has fast distribution and elimination, similar to HPBCD. Interestingly animals could be divided into two groups, where the pharmacokinetic parameters followed or did not follow the two-compartment, first-order kinetic model. Tissue distribution studies revealed, that a significant amount of FITC-HPBCD could be detected in kidneys after 60 min treatment, due to its renal excretion. Ex vivo fluorescent imaging showed that fluorescence could be measured in lung, liver, brain and spleen after 30 min of treatment. To model the interaction and cellular distribution of FITC-HPBCD in the wall of blood vessels, we treated human umbilical vein endothelial cells (HUVECs) with FITC-HPBCD and demonstrated for the first time that this compound could be detected in the cytoplasm in small vesicles after 30 min of treatment. FITC-HPBCD has similar pharmacokinetic to HPBCD and can provide new information to the detailed mechanism of action of HPBCD. View Full-Text
Keywords: hydroxypropyl-beta-cyclodextrin; pharmacokinetics; HUVECs; endocytosis; fluorescence hydroxypropyl-beta-cyclodextrin; pharmacokinetics; HUVECs; endocytosis; fluorescence
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MDPI and ACS Style

Váradi, J.; Hermenean, A.; Gesztelyi, R.; Jeney, V.; Balogh, E.; Majoros, L.; Malanga, M.; Fenyvesi, É.; Szente, L.; Bácskay, I.; Vecsernyés, M.; Fehér, P.; Ujhelyi, Z.; Vasvári, G.; Árvai, I.; Rusznyák, Á.; Balta, C.; Herman, H.; Fenyvesi, F. Pharmacokinetic Properties of Fluorescently Labelled Hydroxypropyl-Beta-Cyclodextrin. Biomolecules 2019, 9, 509. https://doi.org/10.3390/biom9100509

AMA Style

Váradi J, Hermenean A, Gesztelyi R, Jeney V, Balogh E, Majoros L, Malanga M, Fenyvesi É, Szente L, Bácskay I, Vecsernyés M, Fehér P, Ujhelyi Z, Vasvári G, Árvai I, Rusznyák Á, Balta C, Herman H, Fenyvesi F. Pharmacokinetic Properties of Fluorescently Labelled Hydroxypropyl-Beta-Cyclodextrin. Biomolecules. 2019; 9(10):509. https://doi.org/10.3390/biom9100509

Chicago/Turabian Style

Váradi, Judit; Hermenean, Anca; Gesztelyi, Rudolf; Jeney, Viktória; Balogh, Enikő; Majoros, László; Malanga, Milo; Fenyvesi, Éva; Szente, Lajos; Bácskay, Ildikó; Vecsernyés, Miklós; Fehér, Pálma; Ujhelyi, Zoltán; Vasvári, Gábor; Árvai, István; Rusznyák, Ágnes; Balta, Cornel; Herman, Hildegard; Fenyvesi, Ferenc. 2019. "Pharmacokinetic Properties of Fluorescently Labelled Hydroxypropyl-Beta-Cyclodextrin" Biomolecules 9, no. 10: 509. https://doi.org/10.3390/biom9100509

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