Vesicles offer several advantages as vehicles for drug delivery. Encapsulation of a pharmaceutical within spherical layers of lipids affords a diffusion barrier which can be tailored to allow both targeted delivery and sustained release. Assembly of a group of such vesicles within another, outer membrane to form a """"""""vesosome"""""""" would add another level of flexibility, since this procedure could be used to prepare drug cocktails. The proposed plan to investigate the aggregation and subsequent encapsulation of vesicles will further understanding and control of these biomimetic construction processes. The first step, aggregation, results from long-range forces and from crosslinking of receptors in solution with ligands embedded in the lipid walls. Control over the rate and extent of aggregation should be possible by modulating pH, temperature, or ionic strength of the solution or by varying the composition of the vesicles through the addition of polymeric, steric stabilizers. After these conditions have been optimized to afford aggregates of controlled size, metastable sheets of bilayers will be attached by ligand-receptor binding. A simple method such as dialysis or temperature fluctuation will be necessary to make the sheets wrap around the aggregates. Hence, the phase behavior of bilayer membranes will be investigated as a function of composition and temperature. Encapsulation and subsequent release of a fluorescent dye over time will reveal the effectiveness of the membranes as diffusion barriers. These studies will be accomplished using fluorescence spectroscopy to examine the kinetics of ligand-receptor binding, light scattering to determine the rate and extent of aggregation, and transmission electron microscopy to characterize the morphology of the resulting structures.
