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

Song Yang Khor, Jinming Hu, Victoria Mary McLeod, John Quinn, Mark McColl Williamson, Christopher John Porter, Michael Raymond Whittaker, Lisa Michelle Kaminskas, Thomas Paul Davis

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

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 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.
Original languageEnglish
Pages (from-to)2099 - 2108
Number of pages10
JournalNanomedicine-Nanotechnology Biology and Medicine
Volume11
Issue number8
DOIs
Publication statusPublished - 2015

Keywords

  • Biodistribution
  • Cytotoxicity
  • Pharmacokinetics
  • Star polymer
  • Synthesis
  • Tumour biodistribution

Cite this

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title = "Molecular weight (hydrodynamic volume) dictates the systemic pharmacokinetics and tumour disposition of PolyPEG star polymers",
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 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.",
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author = "Khor, {Song Yang} and Jinming Hu and McLeod, {Victoria Mary} and John Quinn and Williamson, {Mark McColl} and Porter, {Christopher John} and Whittaker, {Michael Raymond} and Kaminskas, {Lisa Michelle} and Davis, {Thomas Paul}",
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Molecular weight (hydrodynamic volume) dictates the systemic pharmacokinetics and tumour disposition of PolyPEG star polymers. / Khor, Song Yang; Hu, Jinming; McLeod, Victoria Mary; Quinn, John; Williamson, Mark McColl; Porter, Christopher John; Whittaker, Michael Raymond; Kaminskas, Lisa Michelle; Davis, Thomas Paul.

In: Nanomedicine-Nanotechnology Biology and Medicine, Vol. 11, No. 8, 2015, p. 2099 - 2108.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Khor, Song Yang

AU - Hu, Jinming

AU - McLeod, Victoria Mary

AU - Quinn, John

AU - Williamson, Mark McColl

AU - Porter, Christopher John

AU - Whittaker, Michael Raymond

AU - Kaminskas, Lisa Michelle

AU - Davis, Thomas Paul

PY - 2015

Y1 - 2015

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AB - 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.

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KW - Cytotoxicity

KW - Pharmacokinetics

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KW - Synthesis

KW - Tumour biodistribution

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