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VCAM-1 directed target-sensitive liposomes carrying CCR2 antagonists bind to activated endothelium and reduce adhesion and transmigration of monocytes


Calin, Manuela; Stan, Daniela; Schlesinger, Martin; Simion, Viorel; Deleanu, M; Constantinescu, C; Gan, AM; Pirvulescu, M; Butoi, E; Manduteanu, I; Bota, M; Enachescu, M; Borsig, Lubor; Bendas, Gerd; Simionescu, Maya (2015). VCAM-1 directed target-sensitive liposomes carrying CCR2 antagonists bind to activated endothelium and reduce adhesion and transmigration of monocytes. European Journal of Pharmaceutics and Biopharmaceutics, 89:18-29.

Abstract

Chemokines are critically involved in the development of chronic inflammatory-associated diseases such as atherosclerosis. We hypothesised that targeted delivery of compounds to the surface of activated endothelial cells (EC) interferes with chemokine/receptor interaction and thereby efficiently blocks inflammation. We developed PEGylated target-sensitive liposomes (TSL) encapsulating a CCR2 antagonist (Teijin compound 1) coupled with a specific peptide recognized by endothelial VCAM-1 (Vp-TSL-Tj). TSL were characterized for size (by dynamic light scattering), the amount of peptide coupled at the surface of liposomes and Teijin release (by HPLC). We report that Vp-TSL-Tj binds specifically to activated EC in vitro and in vivo, release the entrapped Teijin and prevent the transmigration of monocytes through activated EC. This is the first evidence that nanocarriers transporting and releasing chemokine inhibitors at specific pathological sites reduce the chemokine-dependent inflammatory process.

Abstract

Chemokines are critically involved in the development of chronic inflammatory-associated diseases such as atherosclerosis. We hypothesised that targeted delivery of compounds to the surface of activated endothelial cells (EC) interferes with chemokine/receptor interaction and thereby efficiently blocks inflammation. We developed PEGylated target-sensitive liposomes (TSL) encapsulating a CCR2 antagonist (Teijin compound 1) coupled with a specific peptide recognized by endothelial VCAM-1 (Vp-TSL-Tj). TSL were characterized for size (by dynamic light scattering), the amount of peptide coupled at the surface of liposomes and Teijin release (by HPLC). We report that Vp-TSL-Tj binds specifically to activated EC in vitro and in vivo, release the entrapped Teijin and prevent the transmigration of monocytes through activated EC. This is the first evidence that nanocarriers transporting and releasing chemokine inhibitors at specific pathological sites reduce the chemokine-dependent inflammatory process.

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5 citations in Web of Science®
5 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:10 January 2015
Deposited On:07 Jan 2016 11:47
Last Modified:05 Apr 2016 19:49
Publisher:Elsevier
ISSN:0939-6411
Funders:SNSF
Publisher DOI:https://doi.org/10.1016/j.ejpb.2014.11.016
PubMed ID:25438248

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