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Title
  • en Advantages of ethanol dilution method for preparing GALA-modified liposomal siRNA carriers on the in vivo gene knockdown efficiency in pulmonary endothelium
Creator
    • en Kusumoto, Kenji
    • en Santiwarangkool, Sarochin
Accessrights open access
Subject
  • Other en Ethanol dilution method
  • Other en siRNA
  • Other en Lung endothelium
  • Other en Intracellular trafficking
  • Other en Lipid nanoparticles
  • NDC 499
Description
  • Abstract en 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.
Publisher en Elsevier Science
Date
    Issued2014-10-01
Language
  • eng
Resource Type journal article
Version Type AM
Identifier HDL http://hdl.handle.net/2115/57444
Relation
  • isVersionOf DOI https://doi.org/10.1016/j.ijpharm.2014.07.007
  • PMID 24998506
Journal
    • PISSN 0378-5173
      • en International Journal of Pharmaceutics
      • Volume Number473 Issue Number1-2 Page Start144 Page End147
File
Oaidate 2023-07-26