Michael Whittaker - Academia.edu (original) (raw)
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Papers by Michael Whittaker
ACS Nano, 2010
A variety of functional polymer chains prepared by RAFT were directly grafted onto 5, 10, and 20 ... more A variety of functional polymer chains prepared by RAFT were directly grafted onto 5, 10, and 20 nm gold nanoparticles (AuNPs). The polymer shell coating the AuNPs was densely packed because of the strong binding between the trithioester groups on the polymer chain-ends and gold. It was found that due to the densely packed nature of the shell the polymer chains were significantly stretched compared to their usual Gaussian coil conformation in water. This was even evident for polymer chains where ionic repulsion between neighboring chains should be significant. Therefore, with such high grafting densities the surface properties and size of the hybrid nanoparticles should be the only contributing factors in cellular uptake in epithelial Caco-2 cells. This study has provided valuable insight into the effects of charge and size of NPs for the application of NPs in the delivery of therapeutic agents across the intestine. Our results showed that the negatively charged AuNPs were taken up by the cells with greater efficiency than the neutral AuNPs, most probably due to binding with membrane proteins.
Nanomedicine : nanotechnology, biology, and medicine, Jan 5, 2015
Herein we report for the first time the biological fate of poly[(oligoethylene glycol) acrylate] ... more 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.
ACS Nano, 2010
A variety of functional polymer chains prepared by RAFT were directly grafted onto 5, 10, and 20 ... more A variety of functional polymer chains prepared by RAFT were directly grafted onto 5, 10, and 20 nm gold nanoparticles (AuNPs). The polymer shell coating the AuNPs was densely packed because of the strong binding between the trithioester groups on the polymer chain-ends and gold. It was found that due to the densely packed nature of the shell the polymer chains were significantly stretched compared to their usual Gaussian coil conformation in water. This was even evident for polymer chains where ionic repulsion between neighboring chains should be significant. Therefore, with such high grafting densities the surface properties and size of the hybrid nanoparticles should be the only contributing factors in cellular uptake in epithelial Caco-2 cells. This study has provided valuable insight into the effects of charge and size of NPs for the application of NPs in the delivery of therapeutic agents across the intestine. Our results showed that the negatively charged AuNPs were taken up by the cells with greater efficiency than the neutral AuNPs, most probably due to binding with membrane proteins.
Nanomedicine : nanotechnology, biology, and medicine, Jan 5, 2015
Herein we report for the first time the biological fate of poly[(oligoethylene glycol) acrylate] ... more 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.