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Intranasal, siRNA Delivery to the Brain by TAT/MGF Tagged PEGylated Chitosan Nanoparticles
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, a...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590831/ https://www.ncbi.nlm.nih.gov/pubmed/26555995 http://dx.doi.org/10.1155/2013/812387 |
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author | Malhotra, Meenakshi Tomaro-Duchesneau, Catherine Saha, Shyamali Prakash, Satya |
author_facet | Malhotra, Meenakshi Tomaro-Duchesneau, Catherine Saha, Shyamali Prakash, Satya |
author_sort | Malhotra, Meenakshi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4590831 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-45908312015-10-13 Intranasal, siRNA Delivery to the Brain by TAT/MGF Tagged PEGylated Chitosan Nanoparticles Malhotra, Meenakshi Tomaro-Duchesneau, Catherine Saha, Shyamali Prakash, Satya J Pharm (Cairo) Research Article 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. Hindawi Publishing Corporation 2013 2013-09-12 /pmc/articles/PMC4590831/ /pubmed/26555995 http://dx.doi.org/10.1155/2013/812387 Text en Copyright © 2013 Meenakshi Malhotra et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Malhotra, Meenakshi Tomaro-Duchesneau, Catherine Saha, Shyamali Prakash, Satya Intranasal, siRNA Delivery to the Brain by TAT/MGF Tagged PEGylated Chitosan Nanoparticles |
title | Intranasal, siRNA Delivery to the Brain by TAT/MGF Tagged PEGylated Chitosan Nanoparticles |
title_full | Intranasal, siRNA Delivery to the Brain by TAT/MGF Tagged PEGylated Chitosan Nanoparticles |
title_fullStr | Intranasal, siRNA Delivery to the Brain by TAT/MGF Tagged PEGylated Chitosan Nanoparticles |
title_full_unstemmed | Intranasal, siRNA Delivery to the Brain by TAT/MGF Tagged PEGylated Chitosan Nanoparticles |
title_short | Intranasal, siRNA Delivery to the Brain by TAT/MGF Tagged PEGylated Chitosan Nanoparticles |
title_sort | intranasal, sirna delivery to the brain by tat/mgf tagged pegylated chitosan nanoparticles |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590831/ https://www.ncbi.nlm.nih.gov/pubmed/26555995 http://dx.doi.org/10.1155/2013/812387 |
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