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Molecular weight (hydrodynamic volume) dictates the systemic pharmacokinetics and tumour disposition of PolyPEG star polymers

Authors :
Lisa M. Kaminskas
Jinming Hu
Christopher J.H. Porter
Michael R. Whittaker
Victoria M. McLeod
Mark Williamson
Thomas P. Davis
John F. Quinn
Song Yang Khor
Source :
Nanomedicine: Nanotechnology, Biology and Medicine. 11:2099-2108
Publication Year :
2015
Publisher :
Elsevier BV, 2015.

Abstract

Herein we report for the first time the biological fate of poly[(oligoethylene glycol) acrylate] (POEGA) star polymers synthesised via a versatile arm-first reversible addition-fragmentation chain transfer (RAFT) polymerisation approach. The biopharmaceutical behaviour of three different molecular weight (49, 64 and 94kDa) POEGA stars was evaluated in rats and nude mice bearing human MDA MB-231 tumours after intravenous administration. The 94kDa star polymer exhibited a longer plasma exposure time than the 49kDa or 64kDa star polymer; an observation attributable to differences in the rates of both polymer biodegradation and urinary excretion. Tumour biodistribution also correlated with molecular weight and was greatest for the longest circulating 94kDa star. Different patterns of liver and spleen biodistribution were observed between mice and rats for the different sized polymers. The polymers were also well-tolerated in vivo and in vitro at therapeutic concentrations. From the Clinical Editor Advances in nanotechnology has enabled scientists to produce nanoparticle as drug carriers in cancer therapeutics. In this article, the authors studied the biological fate of poly[(oligoethylene glycol) acrylate] (POEGA) star polymers of different size, after intravenous injections. This would allow the subsequent comparison to other drug delivery systems for better drug delivery.

Details

ISSN :
15499634
Volume :
11
Database :
OpenAIRE
Journal :
Nanomedicine: Nanotechnology, Biology and Medicine
Accession number :
edsair.doi.dedup.....fea27f8ed7b2a8ec751480683c43ec3f
Full Text :
https://doi.org/10.1016/j.nano.2015.08.001