Analysis of Thiol-sensitive Core-cross-linked Polymeric Micelles Carrying Nucleoside Pendant Groups using ‘On-line’ Methods: Effect of Hydrophobicity on Cross-linking and Degradation
Bianca M. Blunden A B , Donald S. Thomas C and Martina H. Stenzel A DA Centre for Advanced Macromolecular Design (CAMD), School of Chemical Engineering, The University of New South Wales, Sydney, NSW 2052, Australia.
B Cooperative Research Centre (CRC) for Polymers, 8 Redwood Drive, Notting Hill, Vic. 3168, Australia.
C NMR Facility, Mark Wainwright Analytical Centre, The University of New South Wales, Sydney, NSW 2052, Australia.
D Corresponding author. Email: M.Stenzel@unsw.edu.au
Martina Stenzel studied chemistry at the University of Bayreuth, Germany, before completing her Ph.D. in 1999 at the Institute of Applied Macromolecular Chemistry, University of Stuttgart, Germany. With a DAAD scholarship (German Academic Exchange Service) in her pocket, she started working as a postdoctoral Fellow at the UNESCO Centre for Membrane Science and Technology at the University of New South Wales (UNSW), Sydney, Australia. In 2002, she took on a position as a lecturer at the University of New South Wales and worked within the Centre for Advanced Macromolecular Design (CAMD) on complex polymer architectures via RAFT polymerization and honeycomb structured porous films. In 2007, she got promoted Associate Professor. In 2008, she obtained a prestigious ARC Future Fellowship. Her research interest is focussed on the synthesis of functional polymers with complex architectures such as glycopolymers and other polymers for biomedical applications, especially polymers with in-build metal complexes for the delivery of metal-based anti-cancer drugs. Martina Stenzel published more than 150 peer-reviewed papers mainly on RAFT polymerization and 5 book chapters. She is currently the chair of the Polymer division of the Royal Australian Chemical Institute (RACI) and editor of the Australian Journal of Chemistry. She received a range of awards including the 2011 Le Fèvre Memorial Prize. |
Australian Journal of Chemistry 64(6) 766-778 https://doi.org/10.1071/CH10448
Submitted: 8 December 2010 Accepted: 17 March 2011 Published: 27 June 2011
Abstract
Amphiphilic block copolymers were prepared via reversible–addition fragmentation chain transfer (RAFT) polymerization and their synthesis, cross-linking, and degradation were studied using on-line monitoring. The focus of this work is the systematic alteration of the hydrophobic block using copolymers based on 5′-O-methacryloyluridine (MAU) and styrene at different compositions to determine the effect of the copolymer composition on the properties of the micelle. A poly(poly(ethylene glycol) methyl ether methacrylate) (PEGMA) macroRAFT agent was chain extended with a mixture of styrene and MAU. In both systems, an increasing fraction of styrene was found to reduce the rate of polymerization, but the functionality of the RAFT system was always maintained. The amphiphilic block copolymers were dialyzed against water to generate micelles with sizes between 17 and 25 nm according to dynamic light scattering (DLS). Increasing styrene content lead to smaller micelles (determined by DLS and transmission electron microscopy) and to lower critical micelle concentrations, which was measured using surface tensiometry. The micelles were further stabilized via core-cross-linking using bis(2-methacroyloxyethyl) disulfide as crosslinker. NMR analysis revealed a faster consumption of crosslinker with higher styrene content. These stable cross-linked micelles were investigated regarding their ability to degrade in the presence of dithiothreitol as a model reductant. Increasing the styrene content resulted in a faster degradation of the cross-linked micelles into unimers.
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