Biodegradable Microspheres with Enhanced Capacity for Surface Ligand Conjugation

dc.contributor.authorKeegan, Mark E.
dc.descriptionThis item is a DISSERTATION. Committee Chair: W. Mark Saltzman Committee Members: Judith Appleton, Michael Shuleren_US
dc.description.abstractA poly(lactic-co-glycolic acid) (PLGA) microsphere formulation was developed which incorporates carboxylic acid groups into the microsphere surface. These functional groups are suitable for coupling to a variety of ligands, and form linkages that remain stable in aqueous environments for extended periods of time. The ligand binding capacity of these microspheres compares favorably to that of comparably sized carboxylated microspheres, which are commonly used as model particles for targeted microsphere delivery studies. The morphology and drug release kinetics of this PLGA microsphere formulation are not significantly different from those of microspheres made with traditional reagents. A variety of different protein ligands can be conjugated to the surfaces of these microspheres. These microsphere-ligand conjugates were then used in model systems to evaluate the effect of conjugated ligands on microsphere behavior. Microsphere retention in agarose columns was increased by ligands on the microsphere surface specific for receptors on the agarose matrix. In another experiment, conjugating the ligand Ulex europaeus agglutinin 1 to the microsphere surface increased the adhesion of microspheres to Caco-2 monolayers compared to control microspheres. This increase in microsphere adhesion was negated by co-administration of L-fucose, indicating that the increase in adhesion is due to specific interaction of the ligand with carbohydrate receptors on the cell surface. These results demonstrate that the ligands conjugated to the microspheres maintain their receptor binding activity, and are present on the microsphere surface at a density sufficient to target the microspheres to both monolayers and three-dimensional matrices bearing complimentary receptors. These microspheres combine the capability to target specific cell types through surface-conjugated receptors with the ability to release encapsulated drugs over extended periods of time. This combination of properties enhances the utility of biodegradable microspheres for a variety of drug delivery applications.en_US
dc.description.sponsorshipNational Institutes of Health, Air Force Office of Scientific Researchen_US
dc.format.extent1747240 bytes
dc.identifier.citationKeegan, M.E.; Whittum-Hudson, J.A.; Saltzman, W.M.; Biomimetic design in microparticulate vaccines. Biomaterials, v. 24, 2003, 4435-4443en_US
dc.identifier.otherbibid: 6475790
dc.subjectSurface modificationen_US
dc.titleBiodegradable Microspheres with Enhanced Capacity for Surface Ligand Conjugationen_US
dc.typedissertation or thesisen_US
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