タイトル |
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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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作成者 |
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Santiwarangkool, Sarochin
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アクセス権 |
open access |
主題 |
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Other
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Ethanol dilution method
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Other
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siRNA
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Other
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Lung endothelium
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Other
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Intracellular trafficking
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Other
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Lipid nanoparticles
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NDC
499
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内容注記 |
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Abstract
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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.
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出版者 |
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Elsevier Science
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日付 |
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言語 |
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資源タイプ |
journal article |
出版タイプ |
AM |
資源識別子 |
HDL
http://hdl.handle.net/2115/57444
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関連 |
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DOI
https://doi.org/10.1016/j.ijpharm.2014.07.007
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PMID
24998506
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収録誌情報 |
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International Journal of Pharmaceutics
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巻473
号1-2
開始ページ144
終了ページ147
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ファイル |
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コンテンツ更新日時 |
2023-07-26 |