Protection and Systemic Translocation of siRNA Following Oral Administration of Chitosan/siRNA Nanoparticles | Zendy

Borja Ballarín-González | Zendy; Frederik DagnæsHansen | Zendy; Robert A. Fenton | Zendy; Shan Gao | Zendy; San Hein | Zendy; Mingdong Dong | Zendy; Jørgen Kjems | Zendy; Kenneth A. Howard | Zendy

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Protection and Systemic Translocation of siRNA Following Oral Administration of Chitosan/siRNA Nanoparticles

Author(s) -

Borja Ballarín-González,

Frederik DagnæsHansen,

Robert A. Fenton,

Shan Gao,

San Hein,

Mingdong Dong,

Jørgen Kjems,

Kenneth A. Howard

Publication year - 2013

Publication title -

molecular therapy — nucleic acids

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.208

H-Index - 59

ISSN - 2162-2531

DOI - 10.1038/mtna.2013.2

Subject(s) - small interfering rna , chitosan , systemic administration , rna interference , chemistry , nucleic acid , rna , oral administration , microbiology and biotechnology , pharmacology , medicine , biology , biochemistry , in vivo , gene

Harnessing the RNA interference pathway offers a new therapeutic modality; however, solutions to overcome biological barriers to small interfering RNA (siRNA) delivery are required for clinical translation. This work demonstrates, by direct northern and quantitative PCR (qPCR) detection, stability, gastrointestinal (GI) deposition, and translocation into peripheral tissue of nonmodified siRNA after oral gavage of chitosan/siRNA nanoparticles in mice. In contrast to naked siRNA, retained structural integrity and deposition in the stomach, proximal and distal small intestine, and colon was observed at 1 and 5 hours for siRNA within nanoparticles. Furthermore, histological detection of fluorescent siRNA at the apical regions of the intestinal epithelium suggests mucoadhesion provided by chitosan. Detection of intact siRNA in the liver, spleen, and kidney was observed 1 hour after oral gavage, with an organ distribution pattern influenced by nanoparticle N:P ratio that could reflect differences in particle stability. This proof-of-concept work presents an oral delivery platform that could have the potential to treat local and systemic disorders by siRNA

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