title: Use of experimental design methodology for the development of new magnetic siRNA nanovectors (MSN).
abstract: Short interfering RNAs (siRNAs) can downregulate the synthesis of proteins and thus be used to treat certain diseases where the protein synthesis is upregulated, such as cancer. The challenge is to deliver siRNAs in the target cell as they are rapidly degraded by nucleases and have difficulties to cross the cellular membranes. Superparamagnetic iron oxide nanoparticles (SPIONs) are widely studied as platforms for smart biocompatible nanosystems which can be used for magnetic drug targeting and magnetic resonance imaging. The aim of this work was to combine siRNAs, SPIONs, and chitosan, to develop new magnetic siRNA nanovectors suitable for systemic administration. In a first time, the one factor at a time (OFAT) methodology was used to adjust different formulation parameters and to test the feasibility of such a formulation. In a second time, design of experiment (DOE) methodology was used to analyze the influence of these formulation parameters on the physicochemical characteristics hydrodynamic diameter (DH) and ζ-potential. Finally, four MSNs suitable for systemic administration could be identified using the OFAT method. The DOE method showed a significant effect of CR and [NaNO3] on the DH and a significant effect of MR and [siRNA] on the ζ-potential of the nanocarriers.
authors.affiliation: EA 6295 Nanomédicaments et Nanosondes, UFR des Sciences Pharmaceutiques, Université François-Rabelais de Tours, 31 avenue Monge, 37200 Tours, France. stephanie.david@univ-tours.fr
authors.forename: Stephanie
authors.initials: S
authors.lastname: David
authors.forename: Hervé
authors.initials: H
authors.lastname: Marchais
authors.forename: Katel
authors.initials: K
authors.lastname: Hervé-Aubert
authors.forename: Didier
authors.initials: D
authors.lastname: Bedin
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Garin
authors.forename: Claude
authors.initials: C
authors.lastname: Hoinard
authors.forename: Igor
authors.initials: I
authors.lastname: Chourpa
mesh_terms: D005290:Ferric Compounds / Q000737:chemistry*; D018014:Gene Transfer Techniques; D060328:Magnetic Phenomena; D053768:Metal Nanoparticles / Q000737:chemistry*; D009566:Nitrates / Q000737:chemistry; D034741:RNA, Small Interfering / Q000737:chemistry*; D012107:Research Design
chemical_list: D005290:Ferric Compounds; D009566:Nitrates; D034741:RNA, Small Interfering; C000499:ferric oxide; C031618:sodium nitrate
keywords: CR; Chitosan; DOE; MDT; MPS; MR; MRI; MSN; OFAT; Physicochemical characterization; SPIONs; [NaNO(3)]; [siRNA]; charge ratio (chitosan/siRNA); design of experiment; magnetic drug targeting; magnetic resonance imaging; magnetic siRNA nanovectors; mass ratio (iron content of SPIONs/siRNA); mononuclear phagocyte system; one factor at a time; short interfering RNA concentration; siRNA; sodium nitrate concentration; superparamagnetic iron oxide nanoparticles