Chitosan-Mangafodipir nanoparticles designed for intranasal delivery of siRNA and DNA to brain
RNA Therapeutics Institute; Department of Medicine
Genetics and Genomics | Nanomedicine | Neuroscience and Neurobiology | Therapeutics
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.
Gene silencing, Intranasal route, Nanocarrier, Small animal MRI
DOI of Published Version
J Drug Deliv Sci Technol. 2018 Feb;43:453-460. doi: 10.1016/j.jddst.2017.11.013. Epub 2017 Nov 21. Link to article on publisher's site
Journal of drug delivery science and technology
Sanchez-Ramos, Juan; Song, Shijie; Kong, Xiaoyuan; Foroutan, Parastou; Martinez, Gary; Dominguez-Viqueria, William; Mohapatra, Shyam; Mohapatra, Subhra; Haraszti, Reka A.; Khvorova, Anastasia; Aronin, Neil; and Sava, Vasyl, "Chitosan-Mangafodipir nanoparticles designed for intranasal delivery of siRNA and DNA to brain" (2018). RNA Therapeutics Institute Publications. 36.