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Heteromultivalent liposomal nanoconstructs for enhanced targeting and shear-stable binding to active platelets for site-selective vascular drug delivery

Paper ID Volume ID Publish Year Pages File Format Full-Text
7902 568 2011 11 PDF Available
Title
Heteromultivalent liposomal nanoconstructs for enhanced targeting and shear-stable binding to active platelets for site-selective vascular drug delivery
Abstract

Activated platelets play multiple roles in vascular diseases. Hence, a delivery vehicle that can specifically target activated platelets and stay retained under a hemodynamic environment can potentially enhance the efficacy of vehicle-encapsulated vascular drug by protecting it from rapid plasma deactivation, reducing its systemic non-specific side-effects, and increasing its therapeutic index at disease sites undergoing platelet hyperactivity. We rationalized that liposomal nanoconstructs surface-modified with two kinds of peptide that simultaneously bind integrin αIIbβ3 and P-selectin on activated platelets can provide synergistic mechanisms for enhanced selectivity to vascular disease sites. We further hypothesized that dual-receptor targeting will enhance binding strength and retention under flow. We tested this using fluorescently-labeled liposomes, surface-modified by an RGD peptide targeted to active αIIbβ3 and an EWVDV peptide targeted to P-selectin. The liposomes were studied for their platelet-specific interactions inside a parallel plate flow chamber at low-to-high shear stresses. The interaction specificity was further confirmed by flow cytometry. Our results indicate that liposomes surface-modified with both RGD and EWVDV simultaneously have higher selectivity as well as retention to activated platelets under flow compared to liposomes bearing any one peptide type. These results establish the potential of our nanoconstructs for enhanced site-selective drug delivery in vascular diseases.

Keywords
Platelets; Vascular disease; Drug delivery; Liposomes; Flow chamber
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Heteromultivalent liposomal nanoconstructs for enhanced targeting and shear-stable binding to active platelets for site-selective vascular drug delivery
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 35, December 2011, Pages 9504–9514
Authors
, , , , , ,
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