Drug partitioning in individual and mixed micelles and interaction with protein upon delivery form micellar media

Abstract

Poor solubility of drugs has led to the use of drug delivery vehicles to solubilize and to increase the bioavailability of drugs at the target site. Micelles can encapsulate the hydrophobic drugs in their hydrophobic core and thus increase the bioavailability in vivo. Mixed micelles have complementary properties of its individual micelles and can be used as efficient drug delivery vehicles. In the present investigation, we report the partitioning of naproxen (anti-inflammatory) and methimazole (anti-thyroid) drugs in hexadecyltrimethylammonium bromide (HTAB), triton X-100 (TX-100) and their mixed micelles and detailed comparison of partitioning of diclofenac sodium (anti-inflammatory) with these micelles. The interaction of these drugs with transporter protein BSA upon delivery from micellar media was also studied in order to use these micelles as drug delivery vehicles. Quantitative aspects of interactions have been reported in terms of binding constant, standard molar enthalpy and standard molar entropy of interaction obtained from isothermal titration calorimetry (ITC) in combination with pyrene emission fluorescence, dynamic light scattering, and circular dichroism measurements. Diclofenac sodium and naproxen showed better partitioning in mixed micelles than in individual micelles. Binding of diclofenac sodium with BSA was also enhanced upon delivery from HTAB or mixed micelles whereas the binding of naproxen was reduced upon delivery from micellar media than direct delivery. No effect on the binding of methimazole with BSA was observed even upon the delivery from mixed micelles. Detailed analysis on the energetics of interaction of drugs with micelles and further with BSA upon delivery from micellar media can assist in developing effective drug delivery vehicles and also provide guidelines for rational drug design.