title: A fast and sensitive method for measuring the integrity of siRNA-carrier complexes in full human serum.
abstract: 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 (approximately 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.
authors: Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
authors: Kevin
authors: K
authors: Buyens
authors: Bart
authors: B
authors: Lucas
authors: Koen
authors: K
authors: Raemdonck
authors: Kevin
authors: K
authors: Braeckmans
authors: Jo
authors: J
authors: Vercammen
authors: Jelle
authors: J
authors: Hendrix
authors: Yves
authors: Y
authors: Engelborghs
authors: Stefaan C
authors: SC
authors: De Smedt
authors: Niek N
authors: NN
authors: Sanders
mesh_terms: D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008081:Liposomes; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D034741:RNA, Small Interfering / Q000097:blood* / Q000737:chemistry; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence; D013997:Time Factors
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D004337:Drug Carriers; D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane