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Dendritic polyglycerol sulfate as a novel platform for paclitaxel delivery: pitfalls of ester linkage

A. Sousa-Herves, P. Würfel, P. Welker, K. Licha, J. Khandare, R. Haag, M. Calderón – 2015

In this study, dendritic polyglycerol sulfate (dPGS) is evaluated as a delivery platform for the anticancer, tubulin-binding drug paclitaxel (PTX). The conjugation of PTX to dPGS is conducted via a labile ester linkage. A non-sulfated dendritic polyglycerol (dPG) is used as a control, and the labeling with an indocarbocyanine dye (ICC) renders multifunctional conjugates that can be monitored by fluorescence microscopy. The conjugates are characterized by 1H NMR, UV-vis measurements, and RP-HPLC. In vitro cytotoxicity of PTX and dendritic conjugates is evaluated using A549 and A431 cell lines, showing a reduced cytotoxic efficacy of the conjugates compared to PTX. The study of uptake kinetics reveals a linear, non saturable uptake in tumor cells for dPGS-PTX-ICC, while dPG-PTX-ICC is hardly taken up. Despite the marginal uptake of dPG-PTX-ICC, it prompts tubulin polymerization to a comparable extent as PTX. These observations suggest a fast ester hydrolysis and premature drug release, as confirmed by HPLC measurements in the presence of plasma enzymes.

Titel
Dendritic polyglycerol sulfate as a novel platform for paclitaxel delivery: pitfalls of ester linkage
Verfasser
A. Sousa-Herves, P. Würfel, P. Welker, K. Licha, J. Khandare, R. Haag, M. Calderón
Datum
2015
Kennung
10.1039/C4NR04428B
Zitierweise
Nanoscale, 2015, 7, 3923-3932
Art
Text
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