Dendritic polyglycerol sulfate as a novel platform for paclitaxel delivery: pitfalls of ester linkage
Citations Over TimeTop 13% of 2014 papers
Abstract
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 (1)H 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.
Related Papers
- → A TPGS-incorporating nanoemulsion of paclitaxel circumvents drug resistance in breast cancer(2014)88 cited
- → Pharmacologic Sensitivity of Paclitaxel to Its Delivery Vehicles Drives Distinct Clinical Outcomes of Paclitaxel Formulations(2015)44 cited
- Pharmacokinetics of paclitaxel in a hemodialysis patient with advanced gastric cancer： A case report(2006)
- → Synthesis and biological activity of A-nor-paclitaxel analogues(1997)14 cited
- Pharmacokinetic study of paclitaxel in malignant ascites from advanced gastric cancer patients(2006)