title: Intranasal, siRNA Delivery to the Brain by TAT/MGF Tagged PEGylated Chitosan Nanoparticles.
abstract: Neurodegeneration is characterized by progressive loss of structure and function of neurons. Several therapeutic methods and drugs are available to alleviate the symptoms of these diseases. The currently used delivery strategies such as implantation of catheters, intracarotid infusions, surgeries, and chemotherapies are invasive in nature and pose a greater risk of postsurgical complications, which can have fatal side effects. The current study utilizes a peptide (TAT and MGF) tagged PEGylated chitosan nanoparticle formulation for siRNA delivery, administered intranasally, which can bypass the blood brain barrier. The study investigates the optimal dose, duration, biodistribution, and toxicity, of the nanoparticle-siRNA formulation, in-vivo. The results indicate that 0.5 mg/kg of siRNA is delivered successfully to the hippocampus, thalamus, hypothalamus, and Purkinje cells in the cerebellum after 4 hrs of post intranasal delivery. The results indicate maximum delivery to the brain in comparison to other tissues with no cellular toxic effects. This study shows the potential of peptide-tagged PEGylated chitosan nanoparticles to be delivered intranasally and target brain tissue for the treatment of neurological disorders.
authors.affiliation: Biomedical Technology and Cell Therapy Research Laboratory, Departments of Biomedical Engineering, Faculty of Medicine, McGill University, 3775 University Street, Room 311, Lyman Duff Medical Building, Montreal, QC, Canada H3A 2B4.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Malhotra
authors.affiliation: Biomedical Technology and Cell Therapy Research Laboratory, Departments of Biomedical Engineering, Faculty of Medicine, McGill University, 3775 University Street, Room 311, Lyman Duff Medical Building, Montreal, QC, Canada H3A 2B4.
authors.forename: Catherine
authors.initials: C
authors.lastname: Tomaro-Duchesneau
authors.affiliation: Biomedical Technology and Cell Therapy Research Laboratory, Departments of Biomedical Engineering, Faculty of Medicine, McGill University, 3775 University Street, Room 311, Lyman Duff Medical Building, Montreal, QC, Canada H3A 2B4 ; Faculty of Dentistry, McGill University, 3775 University Street, Montreal, QC, Canada H3A 2B2.
authors.forename: Shyamali
authors.initials: S
authors.lastname: Saha
authors.affiliation: Biomedical Technology and Cell Therapy Research Laboratory, Departments of Biomedical Engineering, Faculty of Medicine, McGill University, 3775 University Street, Room 311, Lyman Duff Medical Building, Montreal, QC, Canada H3A 2B4.
authors.forename: Satya
authors.initials: S
authors.lastname: Prakash