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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM020218-02
Application #
6351147
Study Section
Special Emphasis Panel (ZRG1-SB (01))
Program Officer
Ikeda, Richard A
Project Start
2001-01-11
Project End
Budget Start
2001-01-11
Budget End
2002-01-10
Support Year
2
Fiscal Year
2001
Total Cost
$37,516
Indirect Cost
Name
University of California Santa Barbara
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
City
Santa Barbara
State
CA
Country
United States
Zip Code
93106