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Polymeric particles conjugated with a ligand to VCAM-1 exhibit selective, avid, and focal adhesion to sites of atherosclerosis
- Source :
- Biotechnology and Bioengineering. 101:400-407
- Publication Year :
- 2008
- Publisher :
- Wiley, 2008.
-
Abstract
- The increased expression of VCAM-1 on endothelial segments within plaque regions could be used as a target to deliver polymeric drug carriers selectively to sites of atherosclerosis. We probed the hypothesis that polymeric particles conjugated with a ligand for VCAM-1 exhibit selective and avid adhesion to sites of atherosclerosis. Particles made from polystyrene or the biodegradable polymer poly(sebacic acid)-block-polyethylene glycol (PSA-PEG) were conjugated with an antibody to VCAM-1 (alpha-VCAM-1) or IgG (negative control). The particles were injected into the jugular vein of ApoE(-/-) (a murine model of atherosclerosis) or wild type mice and their adhesion to the aorta determined. alpha-VCAM-1 particles exhibited significantly greater adhesion to ApoE(-/-) mouse aorta [32 +/- 5 (mean +/- SEM) particles/mm(2) for polystyrene particles and 31 +/- 7 particles/mm(2) for PSA-PEG particles] compared to the level of adhesion to wild type mouse aorta (18 +/- 1 particles/mm(2) for polystyrene particles and 6 +/- 1 particles/mm(2) for PSA-PEG particles). Within ApoE(-/-) mice, the alpha-VCAM-1 particles exhibited significantly greater adhesion to the aorta (32 +/- 5 particles/mm(2) for polystyrene particles and 31 +/- 7 particles/mm(2) for PSA-PEG particles) compared to the adhesion of IgG particles (1 +/- 1 particles/mm(2) for polystyrene particles and 2 +/- 1 particles/mm(2) for PSA-PEG particles). Detailed analysis of the adhesion revealed that alpha-VCAM-1 particles exhibited focal adhesion to plaque regions, in particular the periphery of the plaques, within the ApoE(-/-) mouse aorta. Combined the data demonstrate that polymeric particles conjugated with a ligand to VCAM-1 exhibit selective, avid and focal adhesion to sites of atherosclerosis providing strong evidence that VCAM-1 ligand bearing polymeric particles could be used for targeting drugs selectively to atherosclerotic tissue.
- Subjects :
- Sebacic acid
Vascular Cell Adhesion Molecule-1
Bioengineering
Conjugated system
Ligands
Applied Microbiology and Biotechnology
Anhydrides
Polyethylene Glycols
Substrate Specificity
Focal adhesion
Mice
chemistry.chemical_compound
Animals
VCAM-1
Aorta
Analysis of Variance
Drug Carriers
Focal Adhesions
Ligand
Antibodies, Monoclonal
Adhesion
Atherosclerosis
Biodegradable polymer
chemistry
Immunology
cardiovascular system
Biophysics
Polystyrenes
Polystyrene
Biotechnology
Subjects
Details
- ISSN :
- 10970290 and 00063592
- Volume :
- 101
- Database :
- OpenAIRE
- Journal :
- Biotechnology and Bioengineering
- Accession number :
- edsair.doi.dedup.....df252108fc71397808f1213b9d172b43