Exploring Barrier Mechanisms Relevant for Drug Therapy

Abstract

Membranes play an important role in the compartmentalization of cells and organs. Up to 500 different lipids have been reported to be present in different biological membranes. The origin and meaning of this diversity is not well understood. Membranes mediate the necessary separation between organizational units, but also provide the possibility to connect them. Overcoming the membrane barriers within the body is a major task for any therapeutic agent. The research of the Wunderli group is concentrated on elucidating the basis of drug–membrane interaction and permeation processes, on unraveling the mechanism of action of multi-substrate membrane transporters such as the multi-drug resistance protein P-glycoprotein (P-gp), and on the modulation of paracellular diffusion. Three major projects are pursued: (1) drug–membrane interaction and permeation studies with liposomes of different lipid composition; (2) studies on the mechanism of action of the P-gp with proteoliposomes; (3) modulation of the tight junctions (TJs) of cell barriers to enhance the paracellular transport of hydrophilic therapeutic entities, e.g. peptides.

Keywords

• Lipid membranes
• Multi-drug resistance
• Partitioning
• Permeation
• Tight junctions