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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8622262/ https://www.ncbi.nlm.nih.gov/pubmed/34834222 http://dx.doi.org/10.3390/pharmaceutics13111807 |
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author | Rehman, Asad Ur Busignies, Virginie Coelho Silva Ribeiro, Marcela Almeida Lage, Nayara Tchoreloff, Pierre Escriou, Virginie Charrueau, Christine |
author_facet | Rehman, Asad Ur Busignies, Virginie Coelho Silva Ribeiro, Marcela Almeida Lage, Nayara Tchoreloff, Pierre Escriou, Virginie Charrueau, Christine |
author_sort | Rehman, Asad Ur |
collection | PubMed |
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 | Online Article Text |
id | pubmed-8622262 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86222622021-11-27 Fate of Tableted Freeze-Dried siRNA Lipoplexes in Gastrointestinal Environment Rehman, Asad Ur Busignies, Virginie Coelho Silva Ribeiro, Marcela Almeida Lage, Nayara Tchoreloff, Pierre Escriou, Virginie Charrueau, Christine Pharmaceutics Article 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. MDPI 2021-10-28 /pmc/articles/PMC8622262/ /pubmed/34834222 http://dx.doi.org/10.3390/pharmaceutics13111807 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rehman, Asad Ur Busignies, Virginie Coelho Silva Ribeiro, Marcela Almeida Lage, Nayara Tchoreloff, Pierre Escriou, Virginie Charrueau, Christine Fate of Tableted Freeze-Dried siRNA Lipoplexes in Gastrointestinal Environment |
title | 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_short | Fate of Tableted Freeze-Dried siRNA Lipoplexes in Gastrointestinal Environment |
title_sort | fate of tableted freeze-dried sirna lipoplexes in gastrointestinal environment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8622262/ https://www.ncbi.nlm.nih.gov/pubmed/34834222 http://dx.doi.org/10.3390/pharmaceutics13111807 |
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