Back to Journals » International Journal of Nanomedicine » Volume 6

A polymeric colchicinoid prodrug with reduced toxicity and improved efficacy for vascular disruption in cancer therapy

Authors Crielaard BJ, van der Wal, Lammers T, Le, Hennink, Schiffelers R, Storm G, Fens

Published 2 November 2011 Volume 2011:6 Pages 2697—2703


Review by Single-blind

Peer reviewer comments 4

Bart J Crielaard1, Steffen van der Wal1, Twan Lammers2, Huong Thu Le1, Wim E Hennink1, Raymond M Schiffelers1, Gert Storm1, Marcel HAM Fens1
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; 2Department of Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany
The first two authors contributed equally to this work.

Abstract: Colchicinoids are very potent tubulin-binding compounds, which interfere with microtubule formation, giving them strong cytotoxic properties, such as cell mitosis inhibition and induction of microcytoskeleton depolymerization. While this makes them promising vascular disrupting agents (VDAs) in cancer therapy, their dose-limiting toxicity has prevented any clinical application for this purpose. Therefore, colchicinoids are considered attractive lead molecules for the development of novel vascular disrupting nanomedicine. In a previous study, a polymeric colchicinoid prodrug that showed favorable hydrolysis characteristics at physiological conditions was developed. In the current study, this polymeric colchicinoid prodrug was evaluated in vitro and in vivo for its toxicity and vascular disrupting potential. Cell viability studies with human umbilical vein endothelial cells, as an in vitro measure for colchicine activity, reflected the degradation kinetics of the prodrug accordingly. Upon intravenous treatment, in vivo, of B16F10 melanoma-bearing mice with colchicine or with the polymeric colchicinoid prodrug, apparent vascular disruption and consequent tumor necrosis was observed for the prodrug but not for free colchicine at an equivalent dose. Moreover, a five-times-higher dose of the prodrug was well tolerated, indicating reduced toxicity. These findings demonstrate that the polymeric colchicinoid prodrug has a substantially improved efficacy/toxicity ratio compared with that of colchicine, making it a promising VDA for cancer therapy.

Keywords: colchicine, prodrug, nanomedicines, cancer, vascular disrupting agents

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]


Readers of this article also read:

A novel EGFR-targeted gene delivery system based on complexes self-assembled by EGF, DNA, and activated PAMAM dendrimers

Yin Z, Liu N, Ma M, Wang L, Hao Y, Zhang X

International Journal of Nanomedicine 2012, 7:4625-4635

Published Date: 24 August 2012

The efficacy of mitochondrial targeting antiresistant epirubicin liposomes in treating resistant leukemia in animals

Men Y, Wang XX, Li RJ, Zhang Y, Tian W, Yao HJ, Ju RJ, Ying X, Zhou J, Li N, Zhang L, Yu Y, Lu WL

International Journal of Nanomedicine 2011, 6:3125-3137

Published Date: 2 December 2011

A new era of cancer treatment: carbon nanotubes as drug delivery tools

Madani SY, Naderi N, Dissanayake O, Tan A, Seifalian AM

International Journal of Nanomedicine 2011, 6:2963-2979

Published Date: 22 November 2011

Biocompatibility of Fe3O4@Au composite magnetic nanoparticles in vitro and in vivo

Li Y, Liu J, Zhong Y, Zhang J, Wang Z, Wang L, An Y, Lin M, Gao Z, Zhang D

International Journal of Nanomedicine 2011, 6:2805-2819

Published Date: 9 November 2011

Influence of surface charge on the potential toxicity of PLGA nanoparticles towards Calu-3 cells

Mura S, Hillaireau H, Nicolas J, Le Droumaguet B, Gueutin C, Zanna S, Tsapis N, Fattal E

International Journal of Nanomedicine 2011, 6:2591-2605

Published Date: 26 October 2011

Convection-enhanced delivery of methotrexate-loaded maghemite nanoparticles

Corem-Salkmon E, Ram Z, Daniels D, Perlstein B, Last D, Salomon S, Tamar G, Shneor R, Guez D, Margel S, Mardor Y

International Journal of Nanomedicine 2011, 6:1595-1602

Published Date: 3 August 2011

Evaluation of injectable silica-embedded nanohydroxyapatite bone substitute in a rat tibia defect model

Xu W, Ganz C, Weber U, Adam M, Holzhüter G, Wolter D, Frerich B, Vollmar B, Gerber T

International Journal of Nanomedicine 2011, 6:1543-1552

Published Date: 2 August 2011

The relationship between cellular adhesion and surface roughness in polystyrene modified by microwave plasma radiation

Biazar E, Heidari M, Asefnezhad A, Montazeri N

International Journal of Nanomedicine 2011, 6:631-639

Published Date: 31 March 2011