Biodistribution and molecular studies on orally administered nanoparticle-AON complexes encapsulated with alginate aiming at inducing dystrophin rescue in mdx mice

Maria Sofia Falzarano, Chiara Passarelli, Elena Bassi, Marina Fabris, Daniela Perrone, Patrizia Sabatelli, Nadir M. Maraldi, Silvia Donà, Rita Selvatici, Paolo Bonaldo, Katia Sparnacci, Michele Laus, Paola Braghetta, Paola Rimessi, Alessandra Ferlini

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number527418
JournalBioMed Research International
Volume2013
DOIs
Publication statusPublished - 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Falzarano, M. S., Passarelli, C., Bassi, E., Fabris, M., Perrone, D., Sabatelli, P., Maraldi, N. M., Donà, S., Selvatici, R., Bonaldo, P., Sparnacci, K., Laus, M., Braghetta, P., Rimessi, P., & Ferlini, A. (2013). Biodistribution and molecular studies on orally administered nanoparticle-AON complexes encapsulated with alginate aiming at inducing dystrophin rescue in mdx mice. BioMed Research International, 2013, [527418]. https://doi.org/10.1155/2013/527418