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BioMed Research International
Volume 2013 (2013), Article ID 527418, 13 pages
Research Article

Biodistribution and Molecular Studies on Orally Administered Nanoparticle-AON Complexes Encapsulated with Alginate Aiming at Inducing Dystrophin Rescue in mdx Mice

1Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy
2Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy
3Department of Biology and Evolution, University of Ferrara, 44121 Ferrara, Italy
4IGM-CNR, Unit of Bologna c/o IOR, 40136 Bologna, Italy
5Department of Biomedical Sciences, University of Padua, 35121 Padua, Italy
6Department of Environmental and Life Sciences INSTM, University of Eastern Piedmont, 15121 Alessandria, Italy
7Department of Medical Sciences, Section of Medical Genetics, University of Ferrara, via Fossato di Mortara 74, 44121 Ferrara, Italy

Received 1 July 2013; Revised 10 October 2013; Accepted 14 October 2013

Academic Editor: Akinori Nakamura

Copyright © 2013 Maria Sofia Falzarano et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


We have previously demonstrated that intraperitoneal injections of 2′-O-methyl-phosphorothioate (2′OMePS) antisense oligoribonucleotides adsorbed onto a cationic core-shell nanoparticles (NPs), termed ZM2, provoke dystrophin restoration in the muscles of mdx mice. The aim of the present work was to evaluate the oral route as an alternative way of administration for ZM2-antisense oligoribonucleotides complexes. The biodistribution and elimination of nanoparticles were evaluated after single and multiple oral doses of IR-dye conjugated nanoparticles. Labeled nanoparticles were tracked in vivo as well as in tissue cryosections, urines and feces by Odyssey infrared imaging system, and revealed a permanence in the intestine and abdominal lymph nodes for 72 hours to 7 days before being eliminated. We subsequently tested alginate-free and alginate-encapsulated ZM2-antisense oligoribonucleotides (AON) complexes orally administered 2 and 3 times per week, respectively, in mdx mice for a total of 12 weeks. Treatment with alginate ZM2-AON induced a slight dystrophin rescue in diaphragm and intestine smooth muscles, while no dystrophin was detected in alginate-free ZM2-AON treated mice. These data encourage further experiments on oral administration testing of NP and AON complexes, possibly translatable in oligoribonucleotides-mediated molecular therapies.