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Polymeric particles conjugated with a ligand to VCAM‐1 exhibit selective, avid, and focal adhesion to sites of atherosclerosis
Author(s) -
Deosarkar Sudhir P.,
Malgor Ramiro,
Fu Jie,
Kohn Leonard D.,
Hanes Justin,
Goetz Douglas J.
Publication year - 2008
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.21885
Subject(s) - adhesion , peg ratio , biophysics , polystyrene , chemistry , polyethylene glycol , cell adhesion , materials science , biochemistry , polymer , biology , organic chemistry , finance , economics
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 (α‐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. α‐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 α‐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 α‐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. Biotechnol. Bioeng. 2008;101: 400–407. © 2008 Wiley Periodicals, Inc.