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Membrane Binding by Active Agents

To identify those drug properties that are important for its pharmacological and biopharmaceutical assessment, membrane-binding studies are superior to other methods (e.g., the measurement of octanol/buffer partition coefficients).

At this Department, such studies have been and are currently carried out for many agents - such as for ascomycin derivatives (PhD thesis by Dr. Margret Fröhlich in collaboration with Novartis Pharma AG, Basel, CH), and especially for bile salts (PhD thesis by Dr. Martin Falk).

In order to enable a faster and more generally applicable procedure for determining the binding of active agents to membranes, our group utilizes a fluorescent dye - laurdan - which intercalates stably within biomembranes. Applying this method, we were already able to quantify the binding of various bile salts to model membranes, as well to determine the solubilization properties of these compounds (PhD theses by Dr. Philipp Tauber and Dr. Alice Theobald).

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Using laurdan-labeled liposomes, we currently investigate the integrative behavior of various pharmaceutically active agents within liposomal membranes (PhD thesis by GescheFörst). The use of further fluorescent markers can disclose both the degree of membrane uptake as well as the localization of the active agent within the membrane. Such data can explain pharmacodynamic and pharmacokinetic drug properties, so that it is already conceivable to implement this method in the context of drug development.

 

 

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