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Advantages of ethanol dilution method for preparing GALA-modified liposomal siRNA carriers on the in vivo gene knockdown efficiency in pulmonary endothelium

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/57444

Title: Advantages of ethanol dilution method for preparing GALA-modified liposomal siRNA carriers on the in vivo gene knockdown efficiency in pulmonary endothelium
Authors: Kusumoto, Kenji Browse this author
Akita, Hidetaka Browse this author →KAKEN DB
Santiwarangkool, Sarochin Browse this author
Harashima, Hideyoshi Browse this author →KAKEN DB
Keywords: Ethanol dilution method
siRNA
Lung endothelium
Intracellular trafficking
Lipid nanoparticles
Issue Date: 1-Oct-2014
Publisher: Elsevier Science
Journal Title: International Journal of Pharmaceutics
Volume: 473
Issue: 1-2
Start Page: 144
End Page: 147
Publisher DOI: 10.1016/j.ijpharm.2014.07.007
PMID: 24998506
Abstract: We previously reported that a multifunctional envelope-type nano device (MEND) modified with a GALA peptide (GALA/MEND) exerted dual functions; effective targeting the pulmonary endothelium and endosomal escape. The GALA/MEND containing encapsulated siRNA was originally prepared by the film coated hydration method (GALA/MENDHyd). However, an ethanol dilution method was found to be more appropriate for scaling up the preparation of this liposomal nanoparticle. In this study, we report on the preparation of a GALA/MEND based on the principal of the ethanol dilution (GALA/MENDEto). The gene knockdown efficiency of the MENDHyd and MENDEt0H without GALA-modification was equivalent regardless of the method used in the preparation. The GALA/MENDEt0H induced more efficient gene silencing in the pulmonary endothelium (ED50; approximately 0.17 mg siRNA/kg) compared to the GALA/ MENDHyd. The GALA/MENDEt0H escaped from endosomes more rapidly than GALA/MENDHyd, while the pharmacokinetics and lung accumulation of GALA/MENDEtcni and GALA/MENDHyd were comparable after i.v. administration. Collectively, the ethanol dilution method improves the function of the GALA/MEND as a lung-targeting siRNA carrier. (C) 2014 Elsevier B.V. All rights reserved.
Type: article (author version)
URI: http://hdl.handle.net/2115/57444
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 秋田 英万

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