The interaction of a β2 adrenoceptor agonist drug with biomimetic cell membrane models: The case of terbutaline sulphate

Abstract

Terbutaline sulphate (TS) is a selective short-acting β2 adrenoceptor agonist used for asthma treatment. The pharmacological activity of TS depends on its binding to the transmembrane protein, β2 adrenoceptor. Thus, the interactions of this drug with biological membranes are expected, affecting its pharmacological activity. Using in vitro models to study the interaction of TS with biological membranes can provide important information about the activity of the drug. Here, liposomes with different lipid compositions were used as biomimetic models of cell membranes to evaluate the effect of composition, complexity, and physical state of membranes on TS-membrane interactions. For that, liposomes containing dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and liposomes containing DMPC and cholesterol (CHOL) were prepared. For the study of TS-membrane interactions, the TS lipophilicity was evaluated in terms of i) partition coefficient; ii) the preferential location of the drug within the membrane; iii) and the effect of TS on the membrane fluidity. The obtained data suggest that TS has an affinity for the lipid membrane, partitioning from the aqueous to the lipid phase. The affinity was dependent on the liposomes' compositions, showing a greater affinity for DMPC membranes than for DMPC:CHOL model. Dynamic light scattering (DLS) results revealed that this is due to the rigidizing effect caused by CHOL molecules. These findings provide valuable insights in the understanding of the complex interaction of TS with biomembrane models as well as the relevance of lipid compositions and membrane structure in such interactions, which may be related to its pharmacological activity and side effects. (c) 2021