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

Eur J Pharm Biopharm. 2015 Jan;89:40-7. doi: 10.1016/j.ejpb.2014.11.015. Epub 2014 Nov 25.


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 °C, comply with requirements for in vivo application.

Keywords: Cationic lipid; E-selectin; Endothelium; Inflammation; Liposome-polycation-DNA; Targeted siRNA delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Chemistry, Pharmaceutical / methods
  • DNA / pharmacology
  • Drug Carriers / pharmacology*
  • Drug Delivery Systems / methods
  • E-Selectin / metabolism
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Lipids / pharmacology
  • Liposomes / pharmacology*
  • Particle Size
  • Polyamines / pharmacology*
  • Polyelectrolytes
  • Pyridinium Compounds / pharmacology*
  • RNA, Small Interfering / pharmacology*
  • Transfection / methods


  • 1-methyl-4-(9-dioleyl)methylpyridinium
  • Drug Carriers
  • E-Selectin
  • Lipids
  • Liposomes
  • Polyamines
  • Polyelectrolytes
  • Pyridinium Compounds
  • RNA, Small Interfering
  • polycations
  • DNA