nanobiotechnology-2018-scientifictracks

5 / 18

Nanobiotechnology 2018
Page 23
Nano Research & Applications
ISSN: 2471-9838
E u r o S c i C o n C o n f e r e n c e o n
Nanotech & Nanobiotechnology
J u l y 1 2 - 1 3 , 2 0 1 8
P a r i s , F r a n c e
The intranasal route of drug delivery has traditionally been used to
administer small, lipophilic drugs that are rapidly absorbed into capillaries
of the nasal epithelium, resulting in rapid onset of CNS actions. Many neuro-
therapeutic agents, especially polynucleotides and proteins, do not readily
cross the blood-brain barrier and cannot survive intact in the gut or blood.
Hence, gene therapy for brain disorders has required direct neurosurgical
microinjection or infusion into brain or cerebrospinal fluid. However, recent
research has demonstrated direct nose-to-brain delivery of relatively large
molecules, including neurotrophins (NGF and insulin-like growth factor [IGF]-
1), neuropeptides, cytokines (interferon β-1b and erythropoietin as well as
polynucleotides (DNA plasmids and genes). The present report describes
development of a novel manganese-chelate nanocarrier system for direct nose-
to-brain delivery of small interfering RNA (siRNA) or DNA. The manganese
(Mn) chelate Mangafodopir served 2 functions: 1) as a marker of the NPs
for intracerebral tracking with magnetic resonance imaging (MRI) and 2) as
a cross-linker of the chitosan matrix in the nanocarrier structure. Using high
field small animal MRI, the Mn-tagged NPs were visualized on T1-weighted
images and were found to penetrate from nasal epitheliaum into olfactory bulb
and across brain regions following intranasal instillation of the nanocarriers.
In addition, Mn content of the nanocarrier did not impede the functional activity
of siRNA directed against green fluorescent protein eGFP in transgenic green
mice. Expression of eGFP mRNA in transgenic green mice was decreased by at
least 50% in four brain regions. Those brain regions also exhibited significantly
increased Mn signal in T1-weighted MR images. In separate experiments, we
showed that mNPs loaded with dsDNA encoding the red fluorescent protein
(RFP) was expressed in corpus striatum and other regions following intranasal
administration. Hence, this novel nanocarrier system permitted in vivo tracking
of the therapeutic agent and was effective in delivering nucleic acid payloads
that exhibited the expected activity in brain tissue.
Biography
Juan Sanchez-Ramos received a PhD in Pharmacology and
Physiology from the University of Chicago and aMedical Degree
(MD) from the University of Illinois. He trained in Neurology
at the University of Chicago and as a Fellow in Movement
Disorders at the University of Miami. Currently, he is a Professor
of Neurology at the University of South Florida in Tampa where
he holds the Helen Ellis Endowed Chair for Parkinson's disease
Research and is Director of the HDSA Center of Excellence
for Huntington’s disease. He is also Medical Director of the
non-profit Parkinson Research Foundation based in Sarasota
FL. In addition to teaching and attending to patients with
Movement Disorders, he has directed basic research projects
in neurodegeneration, neurotoxicology, adult stem cell biology
and presently is focused on novel approaches for non-invasive
delivery of gene therapy to brain.
Nanocarriers for nose-to-brain, non-invasive delivery of gene
therapy
Juan Sanchez-Ramos1 , Shijie Song1 , Xiaoyuan Kong1 , Gary
Martinez2, Shyam Mohapatra3, Subra Mohapatra4 , Reka A
Haraszti5, Anastasia Khvorova5 , Neil Aronin5 , Vasyl Sava1
1University of South Florida, USA
2Moffitt Cancer Center and Research Institute, USA
3Nanomedicine Research Center, USA
4Department of Molecular Medicine, USA
5RNA Therapeutics Institute-UMASS, USA
Juan Sanchez-Ramos et al., Nano Res Appl 2018, Volume 4
DOI: 10.21767/2471-9838-C2-011