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.