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

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

Author information

1
University of Groningen, University Medical Center Groningen, Dept. of Pathology & Medical Biology, Medical Biology Section, Groningen, The Netherlands.
2
University of Groningen, Groningen Biomolecular Sciences and Biotechnology Institute, The Netherlands; Stratingh Institute, University of Groningen, Groningen, The Netherlands.
3
University of Groningen, University Medical Center Groningen, Dept. of Pathology & Medical Biology, Medical Biology Section, Groningen, The Netherlands; Synvolux Therapeutics, Groningen, The Netherlands.
4
University of Groningen, University Medical Center Groningen, Dept. of Pathology & Medical Biology, Medical Biology Section, Groningen, The Netherlands. Electronic address: j.a.a.m.kamps@umcg.nl.

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 °C, comply with requirements for in vivo application.

KEYWORDS:

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

PMID:
25460585
DOI:
10.1016/j.ejpb.2014.11.015
[Indexed for MEDLINE]

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