Interaction of a chloride channel blocker with a lipid bilayer membrane and subsequent effect of addition of submicellar concentrations of bile salt

Abstract

The present study demonstrates the interaction of potential chloride channel blocker drug, namely, 9-methylanthroate (9MA) with dimyristoylphosphatidylcholine (DMPC) lipid bilayer membrane in the solid gel (SG, at 15 °C) and liquid crystalline (LC, at 37 °C) phases of the lipid. Our spectroscopic results reveal a relatively greater degree of partitioning of the drug molecules into the DMPC lipid membrane at 37 °C (LC phase) compared to that at 15 °C (SG phase). Furthermore, the study is extended to explore the interaction of a bile salt (sodium deoxycholate, NaDC) with the DMPC lipid bilayer membrane in the SG as well as LC phase utilizing the environment-sensitive photophysical characteristics of the drug. Our steady-state and time-resolved spectroscopic results are invoked to critically analyze all the possibilities of bile salt-induced modulation of the photophysical behavior of the lipid-bound drug e.g., (i) expulsion of the lipid-bound drug molecules to the bulk aqueous phase upon addition of the bile salt, (ii) redistribution of population of the drug molecules within the lipid membrane and (iii) penetration of water molecules into the lipid bilayer membrane and thereby altering the hydration structure of the membrane. Cumulatively, our results appear to converge on the possibility of bile salt-induced hydration of the interfacial region of the lipid membrane as the actuating mechanism of the lipid-bile salt interaction. It is imperative to state that the present study emphasizes on the interaction of DMPC lipid membrane with the bile salt (NaDC) only in the submicellar concentration regime of NaDC which involves no significant perturbation of the lipid vesicle structure.