(332c) An In Vivo Examination of the Vesosome, a Novel Multi-Compartment Drug Carrier

An optimal drug delivery vehicle should circulate in the body long enough to reach the site of illness or disease and also localize itself at the desired site to consequently deliver its contents at a rate appropriate for maximum therapeutic benefit. It should also possess a large drug loading capacity and retain its contents over the course of treatment. While liposomal systems have experienced success with extending circulation, content retention and controlled release remain problematic. The vesosome ? a large lipid bilayer enclosing many smaller liposomes ? is the most suitable candidate for addressing these issues. The external lipid bilayer offers a second barrier of protection for interior components and also serves as the anchor for active targeting components. Furthermore, internal compartmentalization permits customization of separate environments for multiple therapeutics and release triggers, highlighting the vesosome's potential as a single site, single dose, multiple component drug treatment.

The processes of vesosome formation and functionalization are based on the phase behavior exhibited by homogeneous lipid mixtures. Although slight changes in lipid composition, such as the addition of PEG-lipids or fluorescently-labeled lipids, may have a large impact on the structures that form, vesosome formation can still be achieved using heterogeneous lipid mixtures, a success vital to moving the vesosome toward in vivo studies. A variety of microscopy techniques, including freeze-fracture and cryo transmission electron microscopy as well as fluorescence and confocal microscopy, are used to characterize these functionalized drug carriers.

To assess the viability of the vesosome as a drug carrier, the in vivo lifetimes and biodistribution of various formulations were examined in mice. Our work examines how these properties are affected by lipid composition and the addition of other functional components, including ones for controlled release and active targeting.