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Please use this identifier to cite or link to this item: http://hdl.handle.net/1843/54108
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dc.creatorVirginie Busigniespt_BR
dc.creatorPierre Tchoreloffpt_BR
dc.creatorVirginie Escrioupt_BR
dc.creatorDanielle Campiol Arrudapt_BR
dc.creatorChristine Charrueaupt_BR
dc.creatorMarcela Coelho Silva Ribeiropt_BR
dc.creatorAnne-Marie Lachagèspt_BR
dc.creatorÂngelo Malachias de Souzapt_BR
dc.creatorStéphanie Finetpt_BR
dc.creatorAsad Ur Rehmanpt_BR
dc.creatorPascal Bigeypt_BR
dc.date.accessioned2023-05-29T18:12:46Z-
dc.date.available2023-05-29T18:12:46Z-
dc.date.issued2020-
dc.citation.volume17pt_BR
dc.citation.issue4pt_BR
dc.citation.spage1159pt_BR
dc.citation.epage1169pt_BR
dc.identifier.doihttps://doi.org/10.1021/acs.molpharmaceut.9b01190pt_BR
dc.identifier.issn1543-8392pt_BR
dc.identifier.urihttp://hdl.handle.net/1843/54108-
dc.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.pt_BR
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
dc.languageengpt_BR
dc.publisherUniversidade Federal de Minas Geraispt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.departmentICX - DEPARTAMENTO DE FÍSICApt_BR
dc.publisher.initialsUFMGpt_BR
dc.relation.ispartofMolecular Pharmaceutics-
dc.rightsAcesso Restritopt_BR
dc.subjectRNA interferencept_BR
dc.subjectCationic lipidpt_BR
dc.subjectDelivery systempt_BR
dc.subjectAnionic polymerpt_BR
dc.subject.otherÁcido ribonucleicopt_BR
dc.subject.otherMoléculaspt_BR
dc.titleCompression of vectors for small interfering RNAs delivery: toward oral administration of siRNA lipoplexes in tablet formspt_BR
dc.typeArtigo de Periódicopt_BR
dc.url.externahttps://pubs.acs.org/doi/full/10.1021/acs.molpharmaceut.9b01190pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0001-5686-9301pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0001-9838-728Xpt_BR
dc.identifier.orcidhttps://orcid.org/0000-0001-7768-4605pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0003-1771-1880pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-8703-4283pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-6795-8569pt_BR
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