Fate of Tableted Freeze-Dried siRNA Lipoplexes in Gastrointestinal Environment

The incorporation of siRNA into nanocarriers is mandatory to facilitate its intracellular delivery, as siRNA itself cannot enter cells. However, the incorporation of these nanocarriers into oral, solid dosage forms and their fate in the gastrointestinal environment is yet to be explored. In the pres...

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Autores principales:	Asad Ur Rehman, Virginie Busignies, Marcela Coelho Silva Ribeiro, Nayara Almeida Lage, Pierre Tchoreloff, Virginie Escriou, Christine Charrueau
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	oral delivery RNA interference solid dosage form gel electrophoresis nanocarriers Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/a6ad79c461614beaa6b0084cf999832f
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id	oai:doaj.org-article:a6ad79c461614beaa6b0084cf999832f
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spelling	oai:doaj.org-article:a6ad79c461614beaa6b0084cf999832f2021-11-25T18:40:50ZFate of Tableted Freeze-Dried siRNA Lipoplexes in Gastrointestinal Environment10.3390/pharmaceutics131118071999-4923https://doaj.org/article/a6ad79c461614beaa6b0084cf999832f2021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1807https://doaj.org/toc/1999-4923The incorporation of siRNA into nanocarriers is mandatory to facilitate its intracellular delivery, as siRNA itself cannot enter cells. However, the incorporation of these nanocarriers into oral, solid dosage forms and their fate in the gastrointestinal environment is yet to be explored. In the present work, the fate of, (i) naked siRNA, (ii) freshly prepared siRNA lipoplexes, and (iii) tableted siRNA lipoplexes, in simulated gastric and intestinal fluids was studied. The siRNA, either released from or protected within the lipoplexes, was quantified by gel electrophoresis and siRNA efficacy was assessed in cell transfection. The freshly prepared lipoplexes kept their siRNA load and transfection efficiency totally preserved during 1 h of incubation in simulated gastric fluid at 37 °C. However, in simulated intestinal fluid, despite no release of siRNA from lipoplexes after 6 h of incubation, gene silencing efficacy was dramatically decreased even after 1 h of exposure. The lipoplexes obtained from tablets efficiently protected siRNA in simulated gastric fluid, thus preserving the gene silencing efficacy, whereas their incubation in simulated intestinal fluid resulted in a marked siRNA release and decreased gene silencing efficacy. These results provided a detailed explanation for understanding the fate of siRNA in gastrointestinal conditions, when simply loaded in lipoplexes or formulated in the form of tablets.Asad Ur RehmanVirginie BusigniesMarcela Coelho Silva RibeiroNayara Almeida LagePierre TchoreloffVirginie EscriouChristine CharrueauMDPI AGarticleoral deliveryRNA interferencesolid dosage formgel electrophoresisnanocarriersPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1807, p 1807 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	oral delivery RNA interference solid dosage form gel electrophoresis nanocarriers Pharmacy and materia medica RS1-441
spellingShingle	oral delivery RNA interference solid dosage form gel electrophoresis nanocarriers Pharmacy and materia medica RS1-441 Asad Ur Rehman Virginie Busignies Marcela Coelho Silva Ribeiro Nayara Almeida Lage Pierre Tchoreloff Virginie Escriou Christine Charrueau Fate of Tableted Freeze-Dried siRNA Lipoplexes in Gastrointestinal Environment
description	The incorporation of siRNA into nanocarriers is mandatory to facilitate its intracellular delivery, as siRNA itself cannot enter cells. However, the incorporation of these nanocarriers into oral, solid dosage forms and their fate in the gastrointestinal environment is yet to be explored. In the present work, the fate of, (i) naked siRNA, (ii) freshly prepared siRNA lipoplexes, and (iii) tableted siRNA lipoplexes, in simulated gastric and intestinal fluids was studied. The siRNA, either released from or protected within the lipoplexes, was quantified by gel electrophoresis and siRNA efficacy was assessed in cell transfection. The freshly prepared lipoplexes kept their siRNA load and transfection efficiency totally preserved during 1 h of incubation in simulated gastric fluid at 37 °C. However, in simulated intestinal fluid, despite no release of siRNA from lipoplexes after 6 h of incubation, gene silencing efficacy was dramatically decreased even after 1 h of exposure. The lipoplexes obtained from tablets efficiently protected siRNA in simulated gastric fluid, thus preserving the gene silencing efficacy, whereas their incubation in simulated intestinal fluid resulted in a marked siRNA release and decreased gene silencing efficacy. These results provided a detailed explanation for understanding the fate of siRNA in gastrointestinal conditions, when simply loaded in lipoplexes or formulated in the form of tablets.
format	article
author	Asad Ur Rehman Virginie Busignies Marcela Coelho Silva Ribeiro Nayara Almeida Lage Pierre Tchoreloff Virginie Escriou Christine Charrueau
author_facet	Asad Ur Rehman Virginie Busignies Marcela Coelho Silva Ribeiro Nayara Almeida Lage Pierre Tchoreloff Virginie Escriou Christine Charrueau
author_sort	Asad Ur Rehman
title	Fate of Tableted Freeze-Dried siRNA Lipoplexes in Gastrointestinal Environment
title_short	Fate of Tableted Freeze-Dried siRNA Lipoplexes in Gastrointestinal Environment
title_full	Fate of Tableted Freeze-Dried siRNA Lipoplexes in Gastrointestinal Environment
title_fullStr	Fate of Tableted Freeze-Dried siRNA Lipoplexes in Gastrointestinal Environment
title_full_unstemmed	Fate of Tableted Freeze-Dried siRNA Lipoplexes in Gastrointestinal Environment
title_sort	fate of tableted freeze-dried sirna lipoplexes in gastrointestinal environment
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a6ad79c461614beaa6b0084cf999832f
work_keys_str_mv	AT asadurrehman fateoftabletedfreezedriedsirnalipoplexesingastrointestinalenvironment AT virginiebusignies fateoftabletedfreezedriedsirnalipoplexesingastrointestinalenvironment AT marcelacoelhosilvaribeiro fateoftabletedfreezedriedsirnalipoplexesingastrointestinalenvironment AT nayaraalmeidalage fateoftabletedfreezedriedsirnalipoplexesingastrointestinalenvironment AT pierretchoreloff fateoftabletedfreezedriedsirnalipoplexesingastrointestinalenvironment AT virginieescriou fateoftabletedfreezedriedsirnalipoplexesingastrointestinalenvironment AT christinecharrueau fateoftabletedfreezedriedsirnalipoplexesingastrointestinalenvironment
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Fate of Tableted Freeze-Dried siRNA Lipoplexes in Gastrointestinal Environment

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