Intranasal drug delivery of small interfering RNA targeting Beclin1 encapsulated with polyethylenimine (PEI) in mouse brain to achieve HIV attenuation

Abstract We previously reported that activation of the host autophagic protein, Beclin1, by HIV-1 infection represents an essential mechanism in controlling HIV replication and viral-induced inflammatory responses in microglial cells. Existing antiretroviral therapeutic approaches have been limited...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Myosotys Rodriguez, Jessica Lapierre, Chet Raj Ojha, Ajeet Kaushik, Elena Batrakova, Fatah Kashanchi, Seth M. Dever, Madhavan Nair, Nazira El-Hage
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1d8ea56384f5479588de2d484e112d81
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1d8ea56384f5479588de2d484e112d81
record_format	dspace
spelling	oai:doaj.org-article:1d8ea56384f5479588de2d484e112d812021-12-02T16:06:40ZIntranasal drug delivery of small interfering RNA targeting Beclin1 encapsulated with polyethylenimine (PEI) in mouse brain to achieve HIV attenuation10.1038/s41598-017-01819-92045-2322https://doaj.org/article/1d8ea56384f5479588de2d484e112d812017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01819-9https://doaj.org/toc/2045-2322Abstract We previously reported that activation of the host autophagic protein, Beclin1, by HIV-1 infection represents an essential mechanism in controlling HIV replication and viral-induced inflammatory responses in microglial cells. Existing antiretroviral therapeutic approaches have been limited in their ability to cross the blood-brain barrier effectively and recognize and selectively eliminate persistent HIV-infected brain reservoirs. In the present study and for the first time, the bio-distribution and efficacy of noninvasive intranasal delivery of small interfering RNA (siRNA) against the Beclin1 gene using the cationic linear polyethylenimines (PEI) as a gene carrier was investigated in adult mouse brain. Fluorescein isothiocyanate (FITC)-labeled control siRNA delivered intranasally was found in the cytoplasm of neurons and glial cells of the prefrontal cortex at 4 and 24 hours post-delivery, with no major adverse immune reaction encountered. Intranasal delivery of the siRNA targeting Beclin1 significantly depleted the target protein expression levels in brain tissues with no evidence of toxicity. Binding of siRNA to PEI-polymer was characterized and confirmed by Raman spectroscopy. These results indicate that the intranasal drug delivery allows for the direct delivery of the PEI-siRNA nano-complex to the central nervous system, which could potentially offer an efficient means of gene silencing-mediated therapy in the HIV-infected brain.Myosotys RodriguezJessica LapierreChet Raj OjhaAjeet KaushikElena BatrakovaFatah KashanchiSeth M. DeverMadhavan NairNazira El-HageNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Myosotys Rodriguez Jessica Lapierre Chet Raj Ojha Ajeet Kaushik Elena Batrakova Fatah Kashanchi Seth M. Dever Madhavan Nair Nazira El-Hage Intranasal drug delivery of small interfering RNA targeting Beclin1 encapsulated with polyethylenimine (PEI) in mouse brain to achieve HIV attenuation
description	Abstract We previously reported that activation of the host autophagic protein, Beclin1, by HIV-1 infection represents an essential mechanism in controlling HIV replication and viral-induced inflammatory responses in microglial cells. Existing antiretroviral therapeutic approaches have been limited in their ability to cross the blood-brain barrier effectively and recognize and selectively eliminate persistent HIV-infected brain reservoirs. In the present study and for the first time, the bio-distribution and efficacy of noninvasive intranasal delivery of small interfering RNA (siRNA) against the Beclin1 gene using the cationic linear polyethylenimines (PEI) as a gene carrier was investigated in adult mouse brain. Fluorescein isothiocyanate (FITC)-labeled control siRNA delivered intranasally was found in the cytoplasm of neurons and glial cells of the prefrontal cortex at 4 and 24 hours post-delivery, with no major adverse immune reaction encountered. Intranasal delivery of the siRNA targeting Beclin1 significantly depleted the target protein expression levels in brain tissues with no evidence of toxicity. Binding of siRNA to PEI-polymer was characterized and confirmed by Raman spectroscopy. These results indicate that the intranasal drug delivery allows for the direct delivery of the PEI-siRNA nano-complex to the central nervous system, which could potentially offer an efficient means of gene silencing-mediated therapy in the HIV-infected brain.
format	article
author	Myosotys Rodriguez Jessica Lapierre Chet Raj Ojha Ajeet Kaushik Elena Batrakova Fatah Kashanchi Seth M. Dever Madhavan Nair Nazira El-Hage
author_facet	Myosotys Rodriguez Jessica Lapierre Chet Raj Ojha Ajeet Kaushik Elena Batrakova Fatah Kashanchi Seth M. Dever Madhavan Nair Nazira El-Hage
author_sort	Myosotys Rodriguez
title	Intranasal drug delivery of small interfering RNA targeting Beclin1 encapsulated with polyethylenimine (PEI) in mouse brain to achieve HIV attenuation
title_short	Intranasal drug delivery of small interfering RNA targeting Beclin1 encapsulated with polyethylenimine (PEI) in mouse brain to achieve HIV attenuation
title_full	Intranasal drug delivery of small interfering RNA targeting Beclin1 encapsulated with polyethylenimine (PEI) in mouse brain to achieve HIV attenuation
title_fullStr	Intranasal drug delivery of small interfering RNA targeting Beclin1 encapsulated with polyethylenimine (PEI) in mouse brain to achieve HIV attenuation
title_full_unstemmed	Intranasal drug delivery of small interfering RNA targeting Beclin1 encapsulated with polyethylenimine (PEI) in mouse brain to achieve HIV attenuation
title_sort	intranasal drug delivery of small interfering rna targeting beclin1 encapsulated with polyethylenimine (pei) in mouse brain to achieve hiv attenuation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1d8ea56384f5479588de2d484e112d81
work_keys_str_mv	AT myosotysrodriguez intranasaldrugdeliveryofsmallinterferingrnatargetingbeclin1encapsulatedwithpolyethyleniminepeiinmousebraintoachievehivattenuation AT jessicalapierre intranasaldrugdeliveryofsmallinterferingrnatargetingbeclin1encapsulatedwithpolyethyleniminepeiinmousebraintoachievehivattenuation AT chetrajojha intranasaldrugdeliveryofsmallinterferingrnatargetingbeclin1encapsulatedwithpolyethyleniminepeiinmousebraintoachievehivattenuation AT ajeetkaushik intranasaldrugdeliveryofsmallinterferingrnatargetingbeclin1encapsulatedwithpolyethyleniminepeiinmousebraintoachievehivattenuation AT elenabatrakova intranasaldrugdeliveryofsmallinterferingrnatargetingbeclin1encapsulatedwithpolyethyleniminepeiinmousebraintoachievehivattenuation AT fatahkashanchi intranasaldrugdeliveryofsmallinterferingrnatargetingbeclin1encapsulatedwithpolyethyleniminepeiinmousebraintoachievehivattenuation AT sethmdever intranasaldrugdeliveryofsmallinterferingrnatargetingbeclin1encapsulatedwithpolyethyleniminepeiinmousebraintoachievehivattenuation AT madhavannair intranasaldrugdeliveryofsmallinterferingrnatargetingbeclin1encapsulatedwithpolyethyleniminepeiinmousebraintoachievehivattenuation AT naziraelhage intranasaldrugdeliveryofsmallinterferingrnatargetingbeclin1encapsulatedwithpolyethyleniminepeiinmousebraintoachievehivattenuation
_version_	1718384888961302528

Intranasal drug delivery of small interfering RNA targeting Beclin1 encapsulated with polyethylenimine (PEI) in mouse brain to achieve HIV attenuation

Ejemplares similares