Correlating the Properties of Antibiotics with the Energetics of Partitioning in Colloidal Self-Assemblies and the Effect on the Binding of a Released Drug with a Target Protein.

The bioavailability of drugs and the monitoring of efficient dosage requires drug delivery through suitable vehicles. The partitioning characteristics of the drugs in the delivery vehicles is determined by their molecular features and structure. A quantitative understanding of the partitioning of drugs into delivery media and its subsequent release and binding to the target protein is essential to deriving guidelines for rational drug design. We have studied the partitioning of aminoglycosides and macrolide antibiotic drugs kanamycin, gentamicin, azithromycin, and erythromycin in cationic, nonionic, and the mixture of cationic and nonionic self-assemblies. The quantitative aspects of drug partitioning followed by the monitoring of its interaction with target model protein bovine serum albumin on subsequent release have been performed by using a combination of spectroscopy and high-sensitivity calorimetry. The mechanisms of partitioning have been analyzed on the basis of the values of standard molar enthalpy, entropy, the Gibbs free-energy change, and stoichiometry of interaction. The integrity of the binding sites and the effects of the components of the self-assemblies and the released drug on the serum albumin were analyzed by using differential scanning calorimetry and circular dichroism spectroscopy. The thermodynamic signatures of drug partitioning and subsequent binding to target protein have enabled an in-depth correlation of the structure-property-energetics relationships which are crucial for the broader objective of rational drug design.