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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...

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Autores principales: Malhotra, Meenakshi, Tomaro-Duchesneau, Catherine, Saha, Shyamali, Prakash, Satya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
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.
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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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