Physicochemical insights into the micellar delivery of doxycycline and minocycline to the carrier protein in aqueous environment

Abstract

Physicochemical understanding of the micellar drug delivery is essential for designing efficient drug carrier molecules. An in-depth analysis of the partitioning mechanism of drugs in a quantitative manner and the effects of partitioning on the delivery of drugs through micellar media is a subject of enormous research. This paper focuses on the quantitative measurements of the binding of two antibiotic drugs from tetracycline family, doxycycline and minocycline with the carrier protein human serum albumin (HSA). The partitioning of both the drugs in the micellar system of hexadecyltrimethylammonium bromide (HTAB) and their delivery to HSA through this micellar system was also studied applying spectroscopy and calorimetry. A combination of fluorescence spectroscopy, isothermal titration calorimetry (ITC) and docking studies suggest that both the drugs bind close to Site I of HSA. The ITC results establish that the association of drugs with the protein occurs with an affinity of 103-104 M−1 and the binding is mainly entropy driven. The partitioning mechanisms have been evaluated in terms of the values of the changes in values of standard molar Gibbs free-energy, enthalpy, entropy, and partitioning stoichiometry. The thermodynamic signatures associated with the drug-HSA binding in the presence of HTAB micelles suggest that the partitioning of doxycycline/minocycline in the micelles of HTAB changes their interaction behavior with HSA. These findings provide deep understanding about the micellar drug delivery systems, thereby suggesting their potential applications in strategies for more effective therapeutics.