Chitosan-Mangafodipir nanoparticles designed for intranasal delivery of siRNA and DNA to brain

Juan Sanchez-Ramos, Shijie Song, Xiaoyuan Kong, Parastou Foroutan, Gary Martinez, William Dominguez-Viqueria, Shyam Mohapatra, Subra Mohapatra, Reka A. Haraszti, Anastasia Khvorova, Neil Aronin, Vasyl Sava

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

The overall objective of the present research was to develop a nanocarrier system for non-invasive delivery to brain of molecules useful for gene therapy. Manganese-containing nanoparticles (mNPs) carrying anti-eGFP siRNA were tested in cell cultures of eGFP-expressing cell line of mouse fibroblasts (NIH3T3). The optimal mNPs were then tested in vivo in mice. Following intranasal instillation, mNPs were visualized by 7T MRI throughout brain at 24 and 48 hrs. mNPs were effective in significantly reducing GFP mRNA expression in Tg GFP+ mice in olfactory bulb, striatum, hippocampus and cortex. Intranasal instillation of mNPS loaded with dsDNA encoding RFP also resulted in expression of the RFP in multiple brain regions. In conclusion, mNPs carrying siRNA, or dsDNA were capable of delivering the payload from nose to brain. This approach for delivery of gene therapies to humans, if successful, will have a significant impact on disease-modifying therapeutics of neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)453-460
Number of pages8
JournalJournal of Drug Delivery Science and Technology
Volume43
DOIs
StatePublished - Feb 2018
Externally publishedYes

Keywords

  • Gene silencing
  • Intranasal route
  • Nanocarrier
  • Small animal MRI

ASJC Scopus subject areas

  • Pharmaceutical Science

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