In this project sterically stabilized liposomes will be used for photoinduced fusion. Liposomes will be characterized in which polymerization within the bilayer results in destabilization and release of trapped contents. The basic physical characterization studies will be applied to liposome-cell interaction studies, with the goal of efficient photoinduced delivery of liposomal contents to cells having endocytotic activity. Thus, these studies will have an impact on the use of photosensitized liposomes for the localized delivery of drugs to cells. In this application, experiments are proposed for use of visible light to induce release of trapped agents from sterically stabilized liposomes prepared with lipids containing polyethylene glycol at the surface and polymerizable groups near the end of the chain. In the revision, emphasis has been placed on the biophysical characterization of uncharged PEG-lipids that can be prepared in a short synthetic sequence. Dr. Deborah E. Leckband (Department of Chemical Engineering, University of Illinois) has been added as a collaborator to measure surface forces in monolayers of PEG-lipids.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM040427-05
Application #
2608880
Study Section
Biophysical Chemistry Study Section (BBCB)
Project Start
1992-08-01
Project End
2000-11-30
Budget Start
1997-12-01
Budget End
1998-11-30
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Arizona
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Spratt, Tony; Bondurant, Bruce; O'Brien, David F (2003) Rapid release of liposomal contents upon photoinitiated destabilization with UV exposure. Biochim Biophys Acta 1611:35-43
Mueller, Anja; O'Brien, David F (2002) Supramolecular materials via polymerization of mesophases of hydrated amphiphiles. Chem Rev 102:727-57
Bondurant, B; Mueller, A; O'Brien, D F (2001) Photoinitiated destabilization of sterically stabilized liposomes. Biochim Biophys Acta 1511:113-22
Miller, C R; Clapp, P J; O'Brien, D F (2000) Visible light-induced destabilization of endocytosed liposomes. FEBS Lett 467:52-6
Efremova, N V; Bondurant, B; O'Brien, D F et al. (2000) Measurements of interbilayer forces and protein adsorption on uncharged lipid bilayers displaying poly(ethylene glycol) chains. Biochemistry 39:3441-51
Miller, C R; Bondurant, B; McLean, S D et al. (1998) Liposome-cell interactions in vitro: effect of liposome surface charge on the binding and endocytosis of conventional and sterically stabilized liposomes. Biochemistry 37:12875-83
Miller, C R; Bennett, D E; Chang, D Y et al. (1996) Effect of liposomal composition on photoactivated liposome fusion. Biochemistry 35:11782-90
Bennett, D E; O'Brien, D F (1995) Photoactivated enhancement of liposome fusion. Biochemistry 34:3102-13