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

doi:10.1016/j.ejpb.2014.11.015

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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	40-47
Number of pages	8
Journal	European Journal of Pharmaceutics and Biopharmaceutics
Volume	89
DOIs	https://doi.org/10.1016/j.ejpb.2014.11.015
Publication status	Published - Jan 2015
Externally published	Yes

Keywords

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

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10.1016/j.ejpb.2014.11.015

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

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",

author = "Kowalski, \{Piotr S.\} and Kuninty, \{Praneeth R.\} and Bijlsma, \{Klaas T.\} and Stuart, \{Marc C.A.\} and Leus, \{Niek G.J.\} and Ruiters, \{Marcel H.J.\} and Grietje Molema and Kamps, \{Jan A.A.M.\}",

note = "Publisher Copyright: {\textcopyright} 2014 Published by Elsevier B.V.",

year = "2015",

month = jan,

doi = "10.1016/j.ejpb.2014.11.015",

language = "English",

volume = "89",

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journal = "European Journal of Pharmaceutics and Biopharmaceutics",

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AU - Kowalski, Piotr S.

AU - Kuninty, Praneeth R.

AU - Bijlsma, Klaas T.

AU - Stuart, Marc C.A.

AU - Leus, Niek G.J.

AU - Ruiters, Marcel H.J.

AU - Molema, Grietje

AU - Kamps, Jan A.A.M.

PY - 2015/1

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N2 - 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.

AB - 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.

KW - Cationic lipid

KW - E-selectin

KW - Endothelium

KW - Inflammation

KW - Liposome-polycation-DNA

KW - Targeted siRNA delivery

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ER -

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

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Keywords

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