Interaction of Caffeine with Model Lipid Membranes

[Image: see text] Caffeine is not only a widely consumed active stimulant, but it is also a model molecule commonly used in pharmaceutical sciences. In this work, by performing quartz–crystal microbalance and neutron reflectometry experiments we investigate the interaction of caffeine molecules with a model lipid membrane. We determined that caffeine molecules are not able to spontaneously partition from an aqueous environment, enriched in caffeine, into a bilayer. Caffeine could be however included in solid-supported lipid bilayers if present with lipids during self-assembly. In this case, thanks to surface-sensitive techniques, we determined that caffeine molecules are preferentially located in the hydrophobic region of the membrane. These results are highly relevant for the development of new drug delivery vectors, as well as for a deeper understanding of the membrane permeation role of purine molecules.