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12/17/2009

New method yields better dosage of blood-thinning drugs



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Many biological processes are determined by how various molecules in substances recognize and bind to each other. One such example is our immune defense, which is governed by molecules, called antibodies, that recognize and bind to foreign molecules, called antigens. In this way antibodies neutralize the alien molecules. The antibody recognizes the antigen because the antibody has a socket that perfectly matches the structure of the antigen.

This recognition can be influenced artificially using molecular plastic molding technology. This is done by mixing plastic building blocks with the molecule that is to be bound to. When the plastic has solidified, the molecule is washed away. What is left is an impression that molecules of this sort can then bind to when they encounters the plastic mold. The problem is that you also get a number of impressions that are not so good and that are not recognized very well by the molecules to be bound to. This can be minimized by trying to understand why impressions are formed and then providing the material with the best possible properties to produce accurate impressions. This can involve using the right solvent or the right temperature, for example.

As one part of his research, Björn C. G. Karlsson at the University of Kalmar in Sweden has studied a plastic system with recognition for the anesthetic bupivacaine. He has run experiments examining the basis for the creation impressions and various ways of minimizing rebinding to the inferior impressions. He has found that the conditions that yield the best recognition for bupivacaine are governed by a balance between water-repellent and hydrophilic interaction. He also found that this balance can be influenced by temperature.

During his doctoral work, Björn C. G. Karlsson developed a method involving computer simulations of plastic binding before they are effectuated and mapping the interplay that takes place between bupivacaine and the plastic building blocks. The results of this mapping revealed why impressions vary in quality, but also what possibilities there are to use the computer as a tool in selecting the right conditions for producing molecular plastic molds.

The second part of his doctoral work involves the production of a plastic that recognizes warfarin, which is the active substance in the blood-thinning drug variously known as Waran, Coumadin, Jantoven, Marevan, or Lawarin. By collocating the results of an study of warfarin's fluorescent properties with its ability to bind to the artificial plastic, Björn Karlsson was able to help develop a new method for measuring the warfarin content of blood plasma.

For this method, Björn C. G. Karlsson, together with his supervisor Professor Ian Nicholls and research engineer Annika Rosengren, received second prize in the Skapa (Create) Foundation's innovation competition.

Source: idw/Swedish Research Council



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