Molecular weight (hydrodynamic volume) dictates the systemic pharmacokinetics and tumour disposition of PolyPEG star
Song Yang Khor1, Jinming Hu1, Victoria M McLeod2
1ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia; Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
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.
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