291710 Characterization of Lipid Coated Magnetic Nanoparticles for siRNA Delivery

Monday, October 29, 2012
Hall B (Convention Center )
Eily M. Cournoyer1, Geoffrey D. Bothun1 and Niall G. Howlett2, (1)Department of Chemical Engineering, University of Rhode Island, Kingston, RI, (2)Cell and Molecular Biology, University of Rhode Island, Kingston, RI

Superparamagnetic iron oxide nanoparticles have been given much consideration for their applications for both drug delivery and gene therapy. In the presence of an inhomogeneous magnetic field it has been shown that cationic lipid coated magnetic nanoparticles (L-MNPs) may be used to deliver nucleic acids to mammalian cells, making this an ideal model for the delivery of short interfering RNA (20-21 nucleotides). siRNA is being studied as a promising gene therapeutic agent, as it is an integral part of the RNA induced silencing complex. This project focuses on the development of a well-defined siRNA nanocarrier in order to address aggregation and stability within the system.  Preliminary data suggests that a dual solvent exchange method allows for a controlled formulation of these carriers by gradually adjusting solvent polarity.

Hydrophobic 30nm oleic acid coated iron oxide nanoparticles were coated with a monolayer of varying concentrations of cationic 1,2-dioctadecenoyltrimethylammonium-propane (DOTAP) and a dimyristoylglycerophosphoethanolamine-N-[methoxy(polyethylene glycol)-2000 (PEG-2000). The PEG acts as a stabilizing ligand for the carriers to physically prevent aggregation.  The DOTAP serves as the site of attachment for siRNA.  The 50/50 (PEG-2000/DOTAP) ratio showed the greatest stability after several months of shelf life in the intermediate DMSO phase.  Additional tests are being conducted to characterize the percentage of siRNA attachment.  In the future, the carriers will be used in vitro to test for siRNA uptake and knockdown.

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