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

Autor: Virginie Busignies, Danielle Campiol Arruda, Asad Ur Rehman, Christine Charrueau, Virginie Escriou, Angelo Malachias, Pascal Bigey, Stéphanie Finet, Anne-Marie Lachages, Marcela Coelho Silva Ribeiro, Pierre Tchoreloff
Přispěvatelé: Université de Bordeaux, IPB ENSCBP, CNRS UMR 5295, Institut I2M, Pessac, France, Transferts, écoulements, fluides, énergétique (TREFLE), Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), Institut de Mécanique et d'Ingénierie (I2M), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidade Federal de Minas Gerais [Belo Horizonte] (UFMG), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut de minéralogie et de physique des milieux condensés (IMPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Small interfering RNA
Materials science
[SDV.BIO]Life Sciences [q-bio]/Biotechnology
Administration
Oral
Pharmaceutical Science
Nanoparticle
cationic lipid
02 engineering and technology
delivery system
030226 pharmacology & pharmacy
Cell Line
Suspension (chemistry)
Excipients
Mice
03 medical and health sciences
[SPI]Engineering Sciences [physics]
0302 clinical medicine
RNA interference
X-Ray Diffraction
Oral administration
Nucleic Acids
Scattering
Small Angle
Drug Discovery
Animals
Gene Silencing
structure
Particle Size
RNA
Small Interfering
ComputingMilieux_MISCELLANEOUS
Small-angle X-ray scattering
Bilayer
nanoparticle
tablets
anionic polymer
[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences
021001 nanoscience & nanotechnology
Compression (physics)
Lipids
compression
Freeze Drying
[SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology
Nucleic acid
Molecular Medicine
Powders
0210 nano-technology
Biomedical engineering
Zdroj: Molecular Pharmaceutics
Molecular Pharmaceutics, American Chemical Society, In press, 24 p. ⟨10.1021/acs.molpharmaceut.9b01190⟩
Molecular Pharmaceutics, American Chemical Society, In press, 17 (4), pp.1159-1169. ⟨10.1021/acs.molpharmaceut.9b01190⟩
Molecular Pharmaceutics, American Chemical Society, 2020, 17 (4), pp.1159-1169. ⟨10.1021/acs.molpharmaceut.9b01190⟩
ISSN: 1543-8384
1543-8392
DOI: 10.1021/acs.molpharmaceut.9b01190⟩
Popis: International audience; 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.
Databáze: OpenAIRE
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