Efficient siRNA delivery using novel siRNA-loaded Bubble liposomes and ultrasound

Int J Pharm. 2012 Jan 17;422(1-2):504-9. doi: 10.1016/j.ijpharm.2011.11.023. Epub 2011 Nov 22.

Abstract

Recently, we developed novel polyethyleneglycol (PEG)-modified liposomes (Bubble liposomes; BLs) entrapping an ultrasound (US) imaging gas and reported that the combination of BLs and US was useful for the delivery of siRNA directly into the cytoplasm. However, the results were obtained using a mixture of BLs and naked siRNA. With systemic injections, it is important to control the biodistribution of both BLs and siRNA. In addition, the delivery of siRNA is affected by nuclease degradation after intravenous administration. In this study, we prepared novel siRNA-loaded BLs (si-BLs) using a cationic lipid, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). We demonstrated that siRNA could be loaded onto BLs containing DOTAP and that siRNA-loaded BLs were stable in serum. A specific gene-silencing effect was also achieved by transfection with si-BLs. Thus, the combination of si-BLs with US exposure can be used for delivery of siRNA to a specific tissue via systemic injection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Fatty Acids, Monounsaturated / chemistry
  • Fatty Acids, Monounsaturated / metabolism*
  • Injections
  • Liposomes
  • Luciferases / genetics
  • Luciferases / metabolism
  • Microbubbles*
  • Polyethylene Glycols / chemistry
  • Quaternary Ammonium Compounds / chemistry
  • Quaternary Ammonium Compounds / metabolism*
  • RNA Interference*
  • RNA Stability
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / metabolism*
  • Transfection / methods*
  • Ultrasonics*

Substances

  • Fatty Acids, Monounsaturated
  • Liposomes
  • Quaternary Ammonium Compounds
  • RNA, Small Interfering
  • Polyethylene Glycols
  • Luciferases
  • 1,2-dioleoyloxy-3-(trimethylammonium)propane