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

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

  • Eur J Pharm Biopharm. 2015 Jan;89:18-29. doi: 10.1016/j.ejpb.2014.11.016.
Manuela Calin 1,  Daniela Stan 2,  Martin Schlesinger 3,  Viorel Simion 2,  Mariana Deleanu 2,  Cristina Ana Constantinescu 2,  Ana-Maria Gan 2,  Monica Madalina Pirvulescu 2,  Elena Butoi 2,  Ileana Manduteanu 2,  Marian Bota 4,  Marius Enachescu 4,  Lubor Borsig 5,  Gerd Bendas 3,  Maya Simionescu 2
Affiliations

Affiliations

  • 1 Institute of Cellular Biology and Pathology "N. Simionescu" of the Romanian Academy, Bucharest, Romania. Electronic address: manuela.calin@icbp.ro.
  • 2 Institute of Cellular Biology and Pathology "N. Simionescu" of the Romanian Academy, Bucharest, Romania.
  • 3 Department of Pharmacy, University of Bonn, Bonn, Germany.
  • 4 Center for Surface Science and Nanotechnology, University "Politehnica" of Bucharest, Bucharest, Romania.
  • 5 Institute of Physiology, University of Zürich, Zürich, Switzerland.
PMID: 25438248 DOI: 10.1016/j.ejpb.2014.11.016
Abstract

Chemokines are critically involved in the development of chronic inflammatory-associated diseases such as atherosclerosis. We hypothesized 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 liposomal surface and Teijin release (by HPLC). We report that Vp-TSL-Tj binds specifically to activated EC in vitro and in situ, release the entrapped Teijin and prevent the transmigration of monocytes through activated EC. This is the first evidence that nanocarriers which transport and release chemokine inhibitors at specific pathological sites can reduce chemokine-dependent inflammatory processes.

Keywords

CCR2 antagonist; Endothelium; Monocyte; Target-sensitive liposomes; Targeted drug delivery; VCAM-1.

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