Use of experimental design methodology for the development of new magnetic siRNA nanovectors (MSN)

Autor: Igor Chourpa, Stephanie David, Hervé Marchais, Katel Hervé-Aubert, Anne-Sophie Garin, Didier Bedin, Claude Hoinard
Přispěvatelé: Nanomédicaments et Nanosondes, EA 6295 (NMNS), Université de Tours (UT), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Rok vydání: 2013
Předmět:
Small interfering RNA
MESH: Magnetic Phenomena
Superparamagnetic iron oxide nanoparticles
MESH: Ferric Compounds/chemistry
Metal Nanoparticles
Pharmaceutical Science
MESH: Gene Transfer Techniques
MESH: Metal Nanoparticles/chemistry
Nanotechnology
02 engineering and technology
Ferric Compounds
MESH: RNA
Small Interfering/chemistry
Chitosan
03 medical and health sciences
chemistry.chemical_compound
RNA
Small Interfering
[SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials
030304 developmental biology
0303 health sciences
Nitrates
Chemistry
Magnetic Phenomena
MESH: Research Design
Gene Transfer Techniques
021001 nanoscience & nanotechnology
Biocompatible material
[SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology
Targeted drug delivery
Research Design
Systemic administration
Nanocarriers
0210 nano-technology
Zdroj: International Journal of Pharmaceutics
International Journal of Pharmaceutics, Elsevier, 2013, 454 (2), pp.660-667. ⟨10.1016/j.ijpharm.2013.05.051⟩
ISSN: 0378-5173
DOI: 10.1016/j.ijpharm.2013.05.051
Popis: International audience; 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.
Databáze: OpenAIRE
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