A fast and sensitive method for measuring the integrity of siRNA-carrier complexes in full human serum

SiRNA based therapeutics are currently under investigation for treatment of cancer and viral infections. Upon intravenous administration, the nanoscopic delivery systems which carry the siRNA need to be stable in serum, an aspect which is often overlooked in numerous publications on siRNA delivery s...

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Bibliographic Details
Published in:Journal of controlled release 2008-02, Vol.126 (1), p.67-76
Main Authors: Buyens, Kevin, Lucas, Bart, Raemdonck, Koen, Braeckmans, Kevin, Vercammen, Jo, Hendrix, Jelle, Engelborghs, Yves, De Smedt, Stefaan C., Sanders, Niek N.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cationic liposomes
Complex integrity
Drug Carriers - chemistry
Drug Stability
Electrophoresis, Polyacrylamide Gel
Fatty Acids, Monounsaturated - chemistry
Flourescence fluctuation spectroscopy
General pharmacology
Humans
Kinetics
Liposomes
Medical sciences
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Phosphatidylethanolamines - chemistry
Polyethylene Glycols - chemistry
Quaternary Ammonium Compounds - chemistry
RNA, Small Interfering - blood
RNA, Small Interfering - chemistry
Sensitivity and Specificity
Serum
SiRNA
Spectrometry, Fluorescence
Time Factors
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Summary:SiRNA based therapeutics are currently under investigation for treatment of cancer and viral infections. Upon intravenous administration, the nanoscopic delivery systems which carry the siRNA need to be stable in serum, an aspect which is often overlooked in numerous publications on siRNA delivery systems. Techniques currently available for studying the dissociation of siRNA-liposome complexes are time consuming and incompatible with full serum. We therefore developed a fluorescence fluctuation spectroscopy (FFS) based method which allows to monitor the integrity of siRNA-carrier complexes. The method can very rapidly provide quantitative information on the complex integrity in biological media, like full human serum, and at very low siRNA concentrations (∼ 20 nM siRNA). Information on the integrity of intravenously injected siRNA nanoparticles in serum is crucial. Consequently, the FFS method reported in this work may find broad applicability in the field of siRNA-carrier design.
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2007.10.024