(595d) Partitioning of Surface-Active Peptides Into Lipid-Based Microbubbles

Over the past decade, the ability to design assemblies that are capable of providing a means for site-specific targeting, loading/administration of therapeutics, and visualization by clinical diagnostic imaging modalities has become an attractive avenue for localized drug delivery.  Microbubbles have emerged as a particular subset of such “theranostic” materials due to their intrinsic contrast-enhancing properties in the presence of ultrasonic pressure waves, along with the potential to decorate the surface with various functional molecular entities.  Consisting of a hydrophobic gas core encapsulated by a monolayer of surface-active materials, the lateral interactions of molecules at the gas/liquid interface dictate the overall system properties.  While early formulations of microbubble systems have been composed of mainly lipid and polymer permutations, the advancement of these particles relies on the successful conjugation of targeting/therapeutic species to the surface.  One particular class of bioactive molecules that fulfill a wide degree of functions including, binding, ion/membrane transport, cellular signaling, and catalysis are proteins.  Proteins however, are highly complex biomolecules consisting of numerous intramolecular interactions that promote explicit structural conformations.  This work aims to circumvent the higher order complexity of such structural configurations by designing surface-active peptides that adopt well-defined, alpha-helical secondary structures and are capable of partitioning into the surface of novel lipid/polymer microbubbles.  We have designed amphiphilic peptides that display differing charge distribution down the cylindrical axis of the helix and aim to quantify the influence of charge separation on the lateral phase behavior of the monolayer shell, bubble mechanics, and interfacial ordering.