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^*

^*Corresponding author voor dit werk

Onderzoeksoutput: Article › Academic › peer review

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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.

Originele taal-2	English
Pagina's (van-tot)	40-47
Aantal pagina's	8
Tijdschrift	European Journal of Pharmaceutics and Biopharmaceutics
Volume	89
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1016/j.ejpb.2014.11.015
Status	Published - jan.-2015

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SAINT-liposome-polycation particles, a new carrier for improved delivery of siRNAsFinal publisher's version, 1,3 MBLicentie: Taverne

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@article{2f426711ced64e5db5b68fc4548b41c9,

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 degrees C, comply with requirements for in vivo application. (C) 2014 Published by Elsevier B.V.",

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",

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

year = "2015",

month = jan,

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

language = "English",

volume = "89",

pages = "40--47",

journal = "European Journal of Pharmaceutics and Biopharmaceutics",

issn = "0935-1221",

publisher = "ELSEVIER SCIENCE BV",

number = "1",

}

TY - JOUR

T1 - SAINT-liposome-polycation particles, a new carrier for improved delivery of siRNAs to inflamed endothelial cells

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

Y1 - 2015/1

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 degrees C, comply with requirements for in vivo application. (C) 2014 Published by Elsevier B.V.

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 degrees C, comply with requirements for in vivo application. (C) 2014 Published by Elsevier B.V.

KW - Endothelium

KW - Inflammation

KW - E-selectin

KW - Liposome-polycation-DNA

KW - Targeted siRNA delivery

KW - Cationic lipid

KW - INTRAVENOUS GENE DELIVERY

KW - ANTI-E-SELECTIN

KW - IN-VIVO

KW - TARGETED DELIVERY

KW - O-SOMES

KW - ANTI-VCAM-1

KW - EFFICIENCY

KW - COMPLEXES

KW - PROTAMINE

KW - VECTORS

U2 - 10.1016/j.ejpb.2014.11.015

DO - 10.1016/j.ejpb.2014.11.015

M3 - Article

C2 - 25460585

SN - 0935-1221

VL - 89

SP - 40

EP - 47

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

IS - 1

ER -

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

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