Membrane transport studies: novel methods, model systems and thermodynamics

The work in this thesis shows that it is possible to design a diffusion cell which will allow access to the flux and lag time of a permeant without the need for invasive sampling and that this novel cell is both sensitive and reproducible. It was also shown that the cell could be used in conjunction with both simple model membranes and more complex biological membranes, namely the epidermis. From the data achieved from the cell it was possible to derive a series of equations which allowed access to thermodynamic parameters such as ?H, ?G and ?S. An extension of this calculational approach revealed that manipulation of the van’t Hoff isochore, under the condition where enthalpy is constant over the temperature range, it should be possible to calculate the partition coefficient. Ultimately these parameters can be used in the description of structure activity relationships. The systems described in this thesis are of a complex biological nature consequently the returned data reflect this complexity. In order to utilise the data to their full potential some method for dealing with this complexity was sought. One approach widely discussed in the literature is that of chemometric analysis or soft modelling. Initial studies into the use of chemometric analysis proved positive for the data presented in this thesis, and suggested that formulation contributions from components with close absorbance maxima could be separated