Publication

Cellular handling of a dexamethasone-anti-E-selectin immunoconjugate by activated endothelial cells: Comparison with free dexamethasone

Kok, RJ., Asgeirsdottir, SA., Meijer, DKF. & Molema, G., Nov-2002, In : Pharmaceutical Research. 19, 11, p. 1730-1735 6 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Kok, RJ., Asgeirsdottir, SA., Meijer, DKF., & Molema, G. (2002). Cellular handling of a dexamethasone-anti-E-selectin immunoconjugate by activated endothelial cells: Comparison with free dexamethasone. Pharmaceutical Research, 19(11), 1730-1735.

Author

Kok, RJ ; Asgeirsdottir, SA ; Meijer, DKF ; Molema, G. / Cellular handling of a dexamethasone-anti-E-selectin immunoconjugate by activated endothelial cells : Comparison with free dexamethasone. In: Pharmaceutical Research. 2002 ; Vol. 19, No. 11. pp. 1730-1735.

Harvard

Kok, RJ, Asgeirsdottir, SA, Meijer, DKF & Molema, G 2002, 'Cellular handling of a dexamethasone-anti-E-selectin immunoconjugate by activated endothelial cells: Comparison with free dexamethasone', Pharmaceutical Research, vol. 19, no. 11, pp. 1730-1735.

Standard

Cellular handling of a dexamethasone-anti-E-selectin immunoconjugate by activated endothelial cells : Comparison with free dexamethasone. / Kok, RJ; Asgeirsdottir, SA; Meijer, DKF; Molema, G.

In: Pharmaceutical Research, Vol. 19, No. 11, 11.2002, p. 1730-1735.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Kok RJ, Asgeirsdottir SA, Meijer DKF, Molema G. Cellular handling of a dexamethasone-anti-E-selectin immunoconjugate by activated endothelial cells: Comparison with free dexamethasone. Pharmaceutical Research. 2002 Nov;19(11):1730-1735.


BibTeX

@article{f02a201c894a4ec4a1c5642874a86c27,
title = "Cellular handling of a dexamethasone-anti-E-selectin immunoconjugate by activated endothelial cells: Comparison with free dexamethasone",
abstract = "Purpose. For selective inhibition of endothelial cell activation in chronic inflammation, we have developed a dexamethasone-anti-E-selectin immunoconjugate. The present study was performed to evaluate the cellular handling of this immunoconjugate by activated primary endothelial cells and to compare its drug delivery capacity with free dexamethasone.Methods. The binding, uptake, and degradation of I-125-radiolabeled dexamethasone-anti-E-selectin immunoconjugate by TNFalpha-activated endothelial cells were studied for different time periods and at different concentrations, as well as in the presence of inhibitors for E-selectin binding and lysosomal degradation. Its drug delivery capacity was compared with the uptake of unconjugated H-3-labeled dexamethasone.Results. The immunoconjugate was internalized by E-selectin expressing activated endothelial cells and degraded in the lysosomal compartment. The receptor-mediated binding and uptake was saturable, implying a maximal attainable intracellular concentration of the drug. In contrast, free dexamethasone entered both resting and activated endothelial cells by passive diffusion.Conclusions. The dexamethasone-anti-E-selectin immunoconjugate is capable of selective delivering the coupled drug into activated endothelial cells. This targeting concept enables disease-induced drug delivery in which intracellular concentrations can be reached comparable with those obtained after incubation with 3 muM dexamethasone.",
keywords = "drug targeting, immunoconjugate, activated endothelial cells, lysosomal degradation, chronic inflammation, glucocorticoids, NF-KAPPA-B, INFLAMMATORY DISEASES, MOLECULES, ALBUMIN",
author = "RJ Kok and SA Asgeirsdottir and DKF Meijer and G Molema",
year = "2002",
month = "11",
language = "English",
volume = "19",
pages = "1730--1735",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "SPRINGER/PLENUM PUBLISHERS",
number = "11",

}

RIS

TY - JOUR

T1 - Cellular handling of a dexamethasone-anti-E-selectin immunoconjugate by activated endothelial cells

T2 - Comparison with free dexamethasone

AU - Kok, RJ

AU - Asgeirsdottir, SA

AU - Meijer, DKF

AU - Molema, G

PY - 2002/11

Y1 - 2002/11

N2 - Purpose. For selective inhibition of endothelial cell activation in chronic inflammation, we have developed a dexamethasone-anti-E-selectin immunoconjugate. The present study was performed to evaluate the cellular handling of this immunoconjugate by activated primary endothelial cells and to compare its drug delivery capacity with free dexamethasone.Methods. The binding, uptake, and degradation of I-125-radiolabeled dexamethasone-anti-E-selectin immunoconjugate by TNFalpha-activated endothelial cells were studied for different time periods and at different concentrations, as well as in the presence of inhibitors for E-selectin binding and lysosomal degradation. Its drug delivery capacity was compared with the uptake of unconjugated H-3-labeled dexamethasone.Results. The immunoconjugate was internalized by E-selectin expressing activated endothelial cells and degraded in the lysosomal compartment. The receptor-mediated binding and uptake was saturable, implying a maximal attainable intracellular concentration of the drug. In contrast, free dexamethasone entered both resting and activated endothelial cells by passive diffusion.Conclusions. The dexamethasone-anti-E-selectin immunoconjugate is capable of selective delivering the coupled drug into activated endothelial cells. This targeting concept enables disease-induced drug delivery in which intracellular concentrations can be reached comparable with those obtained after incubation with 3 muM dexamethasone.

AB - Purpose. For selective inhibition of endothelial cell activation in chronic inflammation, we have developed a dexamethasone-anti-E-selectin immunoconjugate. The present study was performed to evaluate the cellular handling of this immunoconjugate by activated primary endothelial cells and to compare its drug delivery capacity with free dexamethasone.Methods. The binding, uptake, and degradation of I-125-radiolabeled dexamethasone-anti-E-selectin immunoconjugate by TNFalpha-activated endothelial cells were studied for different time periods and at different concentrations, as well as in the presence of inhibitors for E-selectin binding and lysosomal degradation. Its drug delivery capacity was compared with the uptake of unconjugated H-3-labeled dexamethasone.Results. The immunoconjugate was internalized by E-selectin expressing activated endothelial cells and degraded in the lysosomal compartment. The receptor-mediated binding and uptake was saturable, implying a maximal attainable intracellular concentration of the drug. In contrast, free dexamethasone entered both resting and activated endothelial cells by passive diffusion.Conclusions. The dexamethasone-anti-E-selectin immunoconjugate is capable of selective delivering the coupled drug into activated endothelial cells. This targeting concept enables disease-induced drug delivery in which intracellular concentrations can be reached comparable with those obtained after incubation with 3 muM dexamethasone.

KW - drug targeting

KW - immunoconjugate

KW - activated endothelial cells

KW - lysosomal degradation

KW - chronic inflammation

KW - glucocorticoids

KW - NF-KAPPA-B

KW - INFLAMMATORY DISEASES

KW - MOLECULES

KW - ALBUMIN

M3 - Article

VL - 19

SP - 1730

EP - 1735

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 11

ER -

ID: 4052347