(479f) Expanding On the In Vivo Capabilities of the Vesosome, a Novel Lipid-Based Drug Delivery Vehicle

Although an optimal drug delivery vehicle should have several properties that are universally desired, such as the ability to localize at the site of disease, deliver contents at a rate appropriate for maximum therapeutic benefit and retain its contents over this timeframe, other characteristics, such as loading capacity and circulation lifetime, may be more or less desirable, based on the type of treatment in question. Liposome-based drug delivery systems have been widely used as drug carriers, both in industry and research, and have proven to be adequate in handling the task even though content retention and controlled release remain problematic. Our group has demonstrated the in vivo viability of the vesosome ? a large lipid bilayer enclosing many smaller liposomes ? and shown that it 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.

Prior work on the vesosome centered around modifying it for in vivo active targeting, a phenomena that requires less than a half hour circulation half-life to be effective. The approximate two-hour half life of the vesosome is more than sufficient for this task, but current the current synthesis has proven problematic for purification of the final product. Since the processes of vesosome formation and functionalization are based on the phase behavior exhibited by homogeneous lipid mixtures, slight changes in lipid composition, such as the addition of PEG-lipids or fluorescently-labeled lipids for active targeting and in vivo imaging, have had a notable impact on the structures that form. However, vesosome formation has still been achieved using heterogeneous lipid mixtures. 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.

Our current work is focused on maintaining a suitable half-life for the vesosome while modifying the synthesis to permit for both increased purity and improved in vivo function. Preliminary in vivo active targeting experiments have shown the viability of the vesosome in directed aggregation at disease sites and formulation changes have shown a new synthesis to maintain a comparable half-life while improving upon product purity. Continuing work on the vesosome focuses on quantifying the effectiveness of active targeting and the implementation of multi-drug encapsulation and delivery.