A thermodynamic approach to understand the partitioning of tetracycline family antibiotics in individual and mixed micellar systems

Abstract

Micelle-mediated drug delivery is an efficient and smart way of delivering drugs to the target sites. This method of drug delivery increases the concentration of the drugs specifically to the affected tissues/organs and hence increases the bioavailability of the drug and reduces the side-effects of the drug. Quantitative understanding of the mechanism of partitioning of drugs in micellar structures is crucial for developing guidelines to design effective drug delivery systems. In this background, we have done quantitative studies of the mechanism of partitioning of four drugs doxycycline, minocycline, tetracycline and oxytetracycline which belong to tetracycline family of antibiotics in the HTAB, TX-100 and mixed surfactant micellar system using isothermal titration calorimetry (ITC). The insights into the partitioning mechanisms have been investigated in a temperature range T = 288.15 K–310.15 K in terms of the values of standard molar enthalpy, standard molar entropy, the standard molar Gibbs free-energy change, and stoichiometry of partitioning. The thermodynamic parameters for the interaction of the drugs with the surfactants suggest involvement of ionic/H-bonding as well as hydrophobic interactions between the drugs and the surfactant micelles and monomers. The effects of the drugs on the critical micellar concentration of the surfactants are studied using ITC and fluorescence spectroscopy. The results are essential in establishing structure-properties-energetics correlations and will help in designing enhanced strategies for improved drug delivery systems.