Thermodynamics of kappa-Carrageenan-Amphiphilic Drug Interaction as Influenced by Specific Counterions and Temperature: A Microcalorimetric and Viscometric Study.

The adsorption of amphiphilic drug molecules to a polyelectrolyte, kappa-carrageenan, has been shown to be related to hydrophobicity of drug and the conformation of the polyanion which in turn can be regulated by choice of counterion. The binding is of a strongly cooperative nature and the degree of cooperativity has been found to be related to the self-aggregation tendency of the drug molecules. This system has been examined by titration microcalorimetry and capillary viscometry to determine the thermodynamics of the binding phenomenon. The titration calorimetry data confirms the trends and conclusions drawn regarding the factors that control the binding. Viscometry shows that although there is a change in size of the polymeric chains when the drug molecules are adsorbed, the effect is primarily due to charge neutralization and not a conformation change. This allows the microcalorimetry data to be analyzed to recover the enthalpy of binding of the drug molecules to the polymer. Earlier published equilibrium binding data has been analyzed to determine the binding constants and free energy changes in the process (-25 to -90 kJ/mol). A phenomenological model has been derived for the cooperative binding process for this purpose. The binding process is primarily enthalpy driven with the major part of enthalpy change (-10 to -40 kJ/mol) arising from the aggregation of bound drug molecules, i.e., from hydrophobic interactions; the process is also entropically favorable. The size of these aggregates in polymer-bound state is of the order of 2-5 molecules of drug, similar to the pre-micellar aggregates of the drugs in solution. Copyright 1998 Academic Press.