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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
| 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)
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Submitter: 秋田 英万
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