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

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• 作者：Song Yang Khor ; BPharmSci(Hons)^a ; ^b ; Jinming Hu ; PhD^a ; ^b ; Victoria M. McLeod ; BSc^b ; John F. Quinn ; PhD^a ; ^b ; Mark Williamson ; PhD^c ; Christopher J.H. Porter ; PhD^a ; ^b ; Michael R. Whittaker ; PhD^a ; ^b ; ^{Michael.whittaker@monash.edu" class="auth_mail" title="E-mail the corresponding author} ; Lisa M. Kaminskas ; PhD^b ; ^{Lisa.kaminskas@monash.edu" class="auth_mail" title="E-mail the corresponding author} ; Thomas P. Davis ; PhD^a ; ^b ; ^d ; ^{thomas.p.davis@monash.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：PEG ; Polyethylene glycol ; RAFT ; Reversible addition fragmentation chain transfer ; PDI ; Polydispersity index ; VDM ; 2-Vinyl-4 ; 4-dimethyl-5-oxazolone ; OEGA ; Oligo(ethylene glycol) methyl ether acrylate ; EPR ; Enhanced permeation and retention ; AIBN ; Azobisisobutyronitrile ; SCK ; Shell cross-linked knedel-like ; DMAC ; N ; N-Dimethylacetamide ; GPC ; Gel permeation chromatography ; TEM ; Transmission electron microscopy ; NMR ; Nuclear magnetic resonance ; MDA ; Malondialdehyde ; ALT ; Alanine transaminase ; AST ; As
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：11
• 期：8
• 页码：2099-2108
• 全文大小：840 K

文摘

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 94 kDa) POEGA stars was evaluated in rats and nude mice bearing human MDA MB-231 tumours after intravenous administration. The 94 kDa star polymer exhibited a longer plasma exposure time than the 49 kDa or 64 kDa 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 94 kDa 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.