Soile Nymark, Helsinki University of Technology

Method for measuring free drug concentration in mammalian neural tissue

The use of functional polymers offers possibilities to deliver drugs to their targets in a controlled way. Drug molecules can be released from polymeric structures in a certain time scale by an external stimulus, such as temperature. Developing controlled drug delivery systems requires a method for measuring drug concentration in polymer solutions accurately. In addition, it would be especially valuable to be able to measure drug concentration in a living tissue.

The aim of this thesis was to develop a method for measuring free drug concentration in mammalian neural tissue at different temperatures. Furthermore, the purpose was to find out how the biocompatibility of various monomers and polymers could be tested reliably. The method developed is based on the monotonic dependence of the photoresponse kinetics of mammalian photoreceptors on the concentration of the model drug (3-isobutyl-1-methylxanthine, IBMX). The changes in the photoresponse kinetics were followed by the electroretinogram (ERG) technique. Isolated retinas of the albino rat (Rattus norvegicus) were used as a preparation.

In this thesis it was observed that the kinetics of linear-range photoresponses of rat rods is proportional to the square root of the concentration of IBMX. The calibration curve (the concentration of IBMX as a function of photoresponse kinetics) was used to determine the amount of IBMX released from polymeric structures in the concentration range 3-300 M. It was also shown that rat retina can be used for the testing of biocompatibility of various molecules as rod photoresponses are very sensitive to potentially hazardous molecules.

As shown in this thesis the mammalian retina can be used as a very sensitive biosensor. The method developed will be described in an international serial publication.