Thermoresponsive, well-defined, poly(vinyl alcohol) co-polymers

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Congdon, Thomas R. ; Shaw, Peter ; Gibson, Matthew I. (2015)

Thermoresponsive polymers have attracted huge interest as adaptable biomaterials based on their reversible solubility behaviour which can be exploited for controlled drug delivery or cellular uptake. The most famous and successful of these is poly(ethylene glycol) (PEG), but the thermal transition temperatures that are practically accessible are not physiologically useful. There are some notable examples of synthetic, responsive, polymers that are highly tunable over a physiologically relevant range, but there is still a need for these to be clinically validated in terms of toxicology and immunogenity for in vivo usage, in addition to their widely used in vitro applications. Poly(vinyl alcohol), PVA, is an appealing biocompatible polymer which is already used for a huge range of biomedical applications. Here, PVA is shown to be a highly tunable, thermoresponsive polymer scaffold. RAFT/MADIX polymerization is used to obtain a library of well-defined polymers between 8 and 50 kDa. Selective alkanoylation of the obtained PVA enabled the effect of side-chains, end-groups and molecular weight on the observable transition temperatures to be studied by turbidimetry. It was found that increasingly hydrophobic side chains (acetyl, propanoyl, butanoyl), or increasing their density led to corresponding decreases in cloud point. PVA with just 10 mol% butanoylation was shown to have a thermal transition temperature close to physiological temperatures (37 °C), compared to 70 mol% for acetylation, with temperatures in between accessible by controlling both the relative degree of functionalization, or by altering the chain length. Finally, a secondary response to esterase enzymes was demonstrated as a route to ‘turn off’ the responsive behaviour on demand. This study suggests that PVA-derived polymers may be a useful platform for responsive biomaterials.\ud
  • References (27)
    27 references, page 1 of 3

    (LCST) and chain length. Several formulations were shown to 14 D. E. Meyer, B. C. Shin, G. A. Kong, M. W. Dewhirst and have transitions temperatures in the physiological range, with A. Chilkoti, J. Controlled Release, 2001, 74, 213.

    the more hydrophobic side groups (butanoyl) only requiring 15 Y. Saaka, R. C. Deller, A. Rodger and M. I. Gibson, Macro10 mol% functionalization compared to 60 mol% for acetate. mol. Rapid Commun., 2012, 33, 779.

    The importance of the end groups was also studied, with 16 S. Salmaso, P. Caliceti, V. Amendola, M. Meneghetti, hydrophobic end-groups shown to dominate the phase tran- J. P. Magnusson, G. Pasparakis and C. Alexander, J. Mater.

    sition such that shorter polymers appeared to give lower LCST Chem., 2009, 19, 1608.

    than longer, which must be considered when investigating 17 J.-F. Lutz, Ö. Akdemir and A. Hoth, J. Am. Chem. Soc., 2006, such properties. Finally, the ability of an esterase to selectively 128, 13046.

    remove the acetate groups, to enable the LCST to be 'switched' 18 M. J. Summers, D. J. Phillips and M. I. Gibson, Chem.

    off was demonstrated. These results show that PVA is a valid Commun., 2013, 49, 4223.

    alternative to traditionally used PNIPAMs, POEGMAs or poly 19 D. J. Phillips and M. I. Gibson, Chem. Commun., 2012, 48, (oxazolines) owing to their highly tunable nature and estab- 1054.

    lished in vivo biocompatibility. 20 J. Shepherd, P. Sarker, K. Swindells, I. Douglas, S. MacNeil, L. Swanson and S. Rimmer, J. Am. Chem. Soc., 2010, 132, 1736.

    21 P. Sarker, J. Shepherd, K. Swindells, I. Douglas, S. MacNeil, Acknowledgements L. Swanson and S. Rimmer, Biomacromolecules, 2010, Equipment used was supported by the Innovative Uses for 12, 1.

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