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

Kusumoto, Kenji

Akita, Hidetaka

Santiwarangkool, Sarochin

Harashima, Hideyoshi

  • Other Ethanol dilution method
  • Other siRNA
  • Other Lung endothelium
  • Other Intracellular trafficking
  • Other Lipid nanoparticles
  • NDC 499
  • 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.
PublisherElsevier Science
Date Issued 2014-10-01
NIItypejournal article
Identifier URI
  • isIdenticalTo PMID 24998506
  • isIdenticalTo DOI
    • ISSN 0378-5173
    • International Journal of Pharmaceutics
    473(1-2), 144-147