Service interruption on Monday 11 July from 12:30 to 13:00: all the sites of the CCSD (HAL, EpiSciences, SciencesConf, AureHAL) will be inaccessible (network hardware connection).
Skip to Main content Skip to Navigation
Journal articles

Compression of vectors for small interfering RNAs delivery: toward oral administration of siRNA lipoplexes in tablet form

Abstract : Currently, most nonviral nucleic acid vectors are in the form of colloidal suspensions administered primarily parenterally. This type of formulation and the mode of administration impose strong constraints such as the size of the administered vectors or the production of sterile preparations. The tablet form provides access to easy oral administration, well accepted by patients; As regards nucleic acid vectors, a dry form represents an advance in terms of stability. Using an optimized lipid-based small interfering RNA-delivery system, we studied the tabletability of a liquid suspension of these vectors. We optimized the conditions of freeze-drying by choosing excipients and process, allowing for the conservation of both the gene-silencing efficacy of the formulated siRNAs and the supramolecular structure of the lipid particulate system. Gene-silencing efficacy was assayed on luciferase-expressing cells and the structure of the siRNA vector in freeze-dried and tablet forms was examined using small-angle X-ray scattering (SAXS) synchrotron radiation. The freeze-dried powders were then mixed with excipients necessary for the good progress of the compression by allowing for a regular supply of the matrix and the reduction of friction. The compression was carried out using a rotary press simulator that allows for complete monitoring of the compression conditions. After compression, formulated siRNAs retained more than 60% of their gene-silencing efficacy. Within the tablets, a specific SAXS signal was detectable and the lamellar and cubic phases of the initial liquid suspension were restored after resuspension of siRNA vectors by disintegration of the tablets. These results show that the bilayer lipid structures of the particles were preserved despite the mechanical constraints imposed by the compression. If such a result could be expected after the freeze-drying step, it was never shown, to our knowledge, that siRNA-delivery systems could retain their efficacy and structure after mechanical stress such as compression. This opens promising perspectives to oral administration of siRNA as an alternative to parenteral administration.
Complete list of metadata
Contributor : pascal bigey Connect in order to contact the contributor
Submitted on : Thursday, October 28, 2021 - 1:26:39 PM
Last modification on : Wednesday, March 23, 2022 - 3:40:45 AM
Long-term archiving on: : Saturday, January 29, 2022 - 7:23:00 PM


Busignies et al.pdf
Files produced by the author(s)



Virginie Busignies, Danielle Campiol Arruda, Christine Charrueau, Marcela Coelho Silva Ribeiro, Anne-Marie Lachagès, et al.. Compression of vectors for small interfering RNAs delivery: toward oral administration of siRNA lipoplexes in tablet form. Molecular Pharmaceutics, American Chemical Society, 2020, 17 (4), pp.1159-1169. ⟨10.1021/acs.molpharmaceut.9b01190⟩. ⟨hal-03407297⟩



Record views


Files downloads