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In vitro characterization of leukocyte mimetic for targeting therapeutics to the endothelium using two receptors

Paper ID Volume ID Publish Year Pages File Format Full-Text
12471 793 2005 9 PDF Available
Title
In vitro characterization of leukocyte mimetic for targeting therapeutics to the endothelium using two receptors
Abstract

Selectins (E- and P-selectin) and other endothelial expressed leukocyte adhesion molecules (ELAMs) are potential targets for site-specific delivery of therapeutics to the vascular endothelium due to their specific and highly regulated expression in vascular disease. It was recently shown that degradable microspheres coated with antibodies against E-selectin or other ELAMs can target inflammation in vivo. However, targeting ELAMs alone cannot differentiate between normal and diseased state, as a basal level of these LAMs are expressed on endothelium in healthy tissues. Furthermore, leukocytes usually employ two separate adhesion molecules in parallel to home to diseased tissues, and we recently quantified the advantages of a two-receptor display for the targeting of leukocyte mimetics (Eniola AO, Willcox PJ, Hammer DA. Interplay between rolling and firm adhesion elucidated with a cell-free system engineered with two distinct receptor–ligand pairs. Biophys J 2003;85:2720–31). Here, we describe a leukocyte mimetic for targeting therapeutics to the vasculature in inflammatory diseases via two receptors, selectin and intercellular cell adhesion molecule-1 (ICAM-1), where biodegradable, polymer microspheres were co-functionalized with the selectin ligand, sialyl LewisX (sLeX), and an antibody against ICAM-1, anti-ICAM-1 (aICAM-1). These two-receptor targeted particles, at given ratios of sLeX/aICAM-1, firmly adhere to substrate surface in flow only when both targeting ligands can interact with their respective receptors, mimicking the multi-step in vivo leukocyte adhesion in inflammation. Thus, we have faithfully recreated the specificity and extent of leukocyte adhesion in a platform that can allow for local delivery of therapeutics.

Keywords
Selectin; ICAM-1; Leukocyte; Inflammation; Drug targeting; Two-receptor targeting; Microspheres; Poly(lactic-co-glycolic acid) (PLGA)
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In vitro characterization of leukocyte mimetic for targeting therapeutics to the endothelium using two receptors
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 26, Issue 34, December 2005, Pages 7136–7144
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us