Selectins as new targets for immunoliposome-mediated drug delivery. A potential way of anti-inflammatory therapy.
Endothelial cell adhesion molecules, which are expressed in response to inflammatory signals to mediate recruitment of leukocytes to sites of inflammation, appear to be excellent targets for drug delivery systems to open new perspectives of antiinflammatory therapies. In this study we describe the preparation and characterization of antibody-coupled liposomes (immunoliposomes) as directed against endothelial (E)-selectins. We have examined the factors affecting the covalent coupling of antibodies to the membrane anchor N-glutaryl-phosphatidylethanolamine via amide bound and have compared them to other coupling procedures. The target sensitivity has been demonstrated in a cell-containing in-vitro model, where liposome binding to selectins under either static, or simulated blood flow conditions was illustrated by using fluorescence microscopical means. It could be shown that even under shear force conditions liposomes selectively accumulate at selectin-containing cells when a specific lipid composition and a certain balance in the lipid/antibody ratio was maintained. Furthermore, the need for polyethylene glycol-derived lipids to sterically stabilize the liposomes for preventing unspecific liposome attachment to cells has been demonstrated.
Department of Pharmacy, Martin Luther University Halle, Germany.
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G
Bendas
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Krause
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Schmidt
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Vogel
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Rothe
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000906:Antibodies; D016466:CHO Cells / Q000378:metabolism; D006224:Cricetinae; D016503:Drug Delivery Systems; D006801:Humans; D018796:Immunoconjugates / Q000378:metabolism*; D008081:Liposomes; D051379:Mice; D019087:Selectins / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D000906:Antibodies; D018796:Immunoconjugates; D008081:Liposomes; D019087:Selectins