CXCL1 microspheres: a novel tool to stimulate arteriogenesis

Vincenza Caolo, Mark Vries, John Zupancich, Marcel Houben, George Mihov, Allard Wagenaar, Geertje Swennen, Yael Nossent, Paul Quax, Dennis Suylen, Ingrid Dijkgraaf, Daniel Molin, Tilman Hackeng, Mark Post*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Web of Science)

Abstract

Context: After arterial occlusion, diametrical growth of pre-existing natural bypasses around the obstruction, i.e. arteriogenesis, is the body's main coping mechanism. We have shown before that continuous infusion of chemokine (C-X-C motif) ligand 1 (CXCL1) promotes arteriogenesis in a rodent hind limb ischemia model. Objective: For clinical translation of these positive results, we developed a new administration strategy of local and sustained delivery. Here, we investigate the therapeutic potential of CXCL1 in a drug delivery system based on microspheres. Materials and methods: We generated poly(ester amide) (PEA) microspheres loaded with CXCL1 and evaluated them in vitro for cellular toxicity and chemokine release characteristics. In vivo, murine femoral arteries were ligated and CXCL1 was administered either intra-arterially via osmopump or intramuscularly encapsulated in biodegradable microspheres. Perfusion recovery was measured with Laser-Doppler. Results: The developed microspheres were not cytotoxic and displayed a sustained chemokine release up to 28 d in vitro. The amount of released CXCL1 was 100-fold higher than levels in native ligated hind limb. Also, the CXCL1-loaded microspheres significantly enhanced perfusion recovery at day 7 after ligation compared with both saline and non-loaded conditions (55.4 +/- 5.0% CXCL1-loaded microspheres versus 43.1 +/- 4.5% non-loaded microspheres; n = 8-9; p
Original languageEnglish
Pages (from-to)2919-2926
JournalDrug Delivery
Volume23
Issue number8
DOIs
Publication statusPublished - Oct 2016

Keywords

  • Chemokines
  • drug delivery systems
  • peripheral artery disease
  • sustained release
  • vascular biology

Cite this