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

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dc.creatorVirginie Busignies
dc.creatorPierre Tchoreloff
dc.creatorVirginie Escriou
dc.creatorDanielle Campiol Arruda
dc.creatorChristine Charrueau
dc.creatorMarcela Coelho Silva Ribeiro
dc.creatorAnne-Marie Lachagès
dc.creatorÂngelo Malachias de Souza
dc.creatorStéphanie Finet
dc.creatorAsad Ur Rehman
dc.creatorPascal Bigey
dc.date.accessioned2023-05-29T18:12:46Z
dc.date.accessioned2025-09-08T23:25:30Z
dc.date.available2023-05-29T18:12:46Z
dc.date.issued2020
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.identifier.doihttps://doi.org/10.1021/acs.molpharmaceut.9b01190
dc.identifier.issn1543-8392
dc.identifier.urihttps://hdl.handle.net/1843/54108
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofMolecular Pharmaceutics
dc.rightsAcesso Restrito
dc.subjectÁcido ribonucleico
dc.subjectMoléculas
dc.subject.otherRNA interference
dc.subject.otherCationic lipid
dc.subject.otherDelivery system
dc.subject.otherAnionic polymer
dc.titleCompression of vectors for small interfering RNAs delivery: toward oral administration of siRNA lipoplexes in tablet forms
dc.typeArtigo de periódico
local.citation.epage1169
local.citation.issue4
local.citation.spage1159
local.citation.volume17
local.description.resumoCurrently, 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.
local.identifier.orcidhttps://orcid.org/0000-0001-5686-9301
local.identifier.orcidhttps://orcid.org/0000-0001-9838-728X
local.identifier.orcidhttps://orcid.org/0000-0001-7768-4605
local.identifier.orcidhttps://orcid.org/0000-0003-1771-1880
local.identifier.orcidhttps://orcid.org/0000-0002-8703-4283
local.identifier.orcidhttps://orcid.org/0000-0002-6795-8569
local.publisher.countryBrasil
local.publisher.departmentICX - DEPARTAMENTO DE FÍSICA
local.publisher.initialsUFMG
local.url.externahttps://pubs.acs.org/doi/full/10.1021/acs.molpharmaceut.9b01190

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