SAINT-liposome-polycation particles, a new carrier for improved delivery of siRNAs to inflamed endothelial cells

Piotr S. Kowalski, Praneeth R. Kuninty, Klaas T. Bijlsma, Marc C. A. Stuart, Niek G. J. Leus, Marcel H. J. Ruiters, Grietje Molema, Jan A. A. M. Kamps*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)

Abstract

Interference with acute and chronic inflammatory processes by means of delivery of siRNAs into microvascular endothelial cells at a site of inflammation demands specific, non-toxic and effective siRNA delivery system. In the current work we describe the design and characterization of siRNA carriers based on cationic pyridinium-derived lipid 1-methyl-4-(cis-9-dioleyl)methyl-pyridinium-chloride) (SAINT-C18) and the transfection enhancer protamine, complexed with siRNA/carrier DNA or siRNA only. These carriers, called SAINT-liposome-polycation-DNA (S-LPD) and SAINT-liposome-polycation (S-LP), have a high efficiency of siRNA encapsulation, low cellular toxicity, and superior efficacy of gene downregulation in endothelial cells in vitro as compared to DOTAP-LPD. Incorporation of 10 mol% PEG and anti-E-selectin antibody in these formulations resulted in selective siRNA delivery into activated endothelial cells. Furthermore, we showed that the physicochemical characteristics of S-LPD and S-LP, including size-stability and maintenance of the siRNA integrity in the presence of serum at 37 degrees C, comply with requirements for in vivo application. (C) 2014 Published by Elsevier B.V.

Original languageEnglish
Pages (from-to)40-47
Number of pages8
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume89
Issue number1
DOIs
Publication statusPublished - Jan-2015

Keywords

  • Endothelium
  • Inflammation
  • E-selectin
  • Liposome-polycation-DNA
  • Targeted siRNA delivery
  • Cationic lipid
  • INTRAVENOUS GENE DELIVERY
  • ANTI-E-SELECTIN
  • IN-VIVO
  • TARGETED DELIVERY
  • O-SOMES
  • ANTI-VCAM-1
  • EFFICIENCY
  • COMPLEXES
  • PROTAMINE
  • VECTORS

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