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Morphology studies on warfarin imprinted polymers: the significance of the degree of crosslinking on polymer performance
Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. (BBCL)
Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. (BBCL)ORCID iD: 0000-0002-7392-0591
Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. (BBCL)ORCID iD: 0000-0002-0407-6542
2010 (English)Conference paper, Published paper (Refereed)
Abstract [en]

Warfarin is an oral anticoagulant drug, used in the treatment of thrombolic disorders.1 Since the therapeutic window of warfarin is narrow, careful monitoring of the effect of drug dosage is important. To date, the effect of warfarin treatment is monitored indirectly in which the clotting time (prothrombin time) is measured. The development of an alternative method, ideally both more robust and more sensitive, for the determination of warfarin effect on blood coagulation is desirable.

It was envisaged that a warfarin-selective synthetic antibody prepared by molecular imprinting2 could provide the basis for the development of a novel method to facilitate the direct determination of warfarin in blood, and ideally even allow correlation the extent of patient blood coagulation. A large number of factors have been shown to be important and influence molecularly imprinted polymer (MIP) performance, such as type and amount of monomer incorporated in the final MIP matrix as well as rebinding media.3,4 Recent studies on polymer composition have pointed at the influence of the choice of monomer and template on the textural properties of a MIP.5-7

We have prepared a series of warfarin imprinted methacrylic acid ethylene dimethacrylate co-polymers, with varying degrees of crosslinking, using a non-covalent molecular imprinting strategy. Characterization of polymer morphology and MIP-ligand radioligand binding studies were performed in order to understand the molecular basis for recognition in warfarin MIPs and to optimize polymer composition. Furthermore, we conclude that polymers prepared with a high degree of cross-linking demonstrated the highest binding capacity, however this rebinding is proposed to be predominately non-specific in character. In contrast, the co-existence of specific and non-specific binding was found within polymers with meso- and macroporous size distributions. Finally, detailed investigations of warfarin-MIP rebinding revealed that the optimal polymer composition was represented by a material with a narrow population of pores (~3-4 nm), a size range similar to the diameter of warfarin (~1 nm).

(1)      Landefeld, C.; Beyth, R. Anticoagulant-related bleeding - epidemiology, prediction and prevention. American Journal of Medicine 1993, 95, 315-328

(2)      Alexander, C.; Andersson, H.S.; Andersson, L.I.; Ansell, R.J.; Kirsch, N.; Nicholls, I.A.; O'Mahony, J.; Whitcombe, M.J. Molecular imprinting science and technology: A survey of the literature for the years up to and including 2003. Journal of Molecular Recognition 2006, 19, 106-180.

(3)      Kempe, H.; Kempe, M. Novel method for the synthesis of molecularly imprinted polymer bead libraries. Macromolecular Rapid Communications 2004, 25, 315-320.

(4)      Rosengren, A.M.; Karlsson, J.G.; Andersson, P.O.; Nicholls, I.A. Chemometric models of template-molecularly imprinted polymer binding. Analytical Chemistry 2005, 77, 5700-5705.

(5)      O'Mahony, J.; Molinelli, A.; Nolan, K.; Smyth, M.; Mizaikoff, B. Anatomy of a successful imprint: Analysing the recognition mechanisms of a molecularly imprinted polymer for quercetin. Biosensors and Bioelectronics 2006, 21, 1383-1392.

(6)      Al Kobaisi, M.; Tate, M.; Rix, C.; Jakubov, T.; Mainwaring, D. The effect of molecular imprinting on the pore size distribution of polymers. Adsorption 2007, 13, 315-321.

(7)      Urraca, J. L.; Carbajo, M. C.; Torralvo, M. J.; González-Vázquez, J.; Orellana, G.; Moreno-Bondi, M. C. Effect of the template and functional monomer on the textural properties of molecularly imprinted polymers. Biosensors and Bioelectronics 2008, 24, 155-161.

Place, publisher, year, edition, pages
2010.
National Category
Organic Chemistry
Research subject
Natural Science, Organic Chemistry
Identifiers
URN: urn:nbn:se:lnu:diva-6723OAI: oai:DiVA.org:lnu-6723DiVA, id: diva2:329046
Conference
MIP2010: The 6th International Conference on Molecular Imprinting, New Orleans
Available from: 2010-07-07 Created: 2010-07-07 Last updated: 2016-11-11Bibliographically approved

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Rosengren, Annika M.Karlsson, Björn C. G.Nicholls, Ian A.

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