Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 422, Issue 1-2, Pages 504-509Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2011.11.023
Keywords
siRNA delivery; Ultrasound; Bubble liposomes
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Funding
- New Energy and Industrial Technology Development Organization (NEDO) of Japan [04A05010]
- Japan Society for the Promotion of Science [18650146, 20300179, 21790164]
- Grants-in-Aid for Scientific Research [21790164, 18650146] Funding Source: KAKEN
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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. (C) 2011 Elsevier B. V. All rights reserved.
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