Factors influencing transfection efficiency of pIDUA/nanoemulsion complexes in a mucopolysaccharidosis type I murine model
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/172598 |
Resumo: | Mucopolysaccharidosis type I (MPS I) is an autosomal disease caused by alpha-l-iduronidase (IDUA) deficiency. This study used IDUA knockout mice as a model to evaluate whether parameters such as dose of plasmid and time of treatment could influence the transfection efficiency of complexes formed with PEGylated cationic nanoemulsions and plasmid (pIDUA), which contains the gene that encodes for IDUA. Formulations were composed of medium chain triglycerides, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(amino[polyethylene glycol]-2000), 1,2-dioleoyl-sn-glycero-3-trimethylammonium propane (DOTAP), glycerol, and water and were prepared by the adsorption or encapsulation of preformed pIDUA–DOTAP complexes by high-pressure homogenization. A progressive increase in IDUA expression was observed with an increase in the dose and time of transfection for mice treated with both complexes (adsorbed and encapsulated), especially in the liver. Regardless of the complex administered, a significant increase in IDUA activity was detected in lungs and liver compared with nontreated MPS I when a dose of 60 μg was administered and IDUA activity was measured 7 days postadministration. Tissue sections of major organs showed no presence of cell necrosis, inflammatory infiltrate, or an increase in apoptosis. Furthermore, immunohistochemistry for CD68 showed no difference in the number of macrophage cells in treated and nontreated animals, indicating the absence of inflammatory reaction caused by the treatment. The data set obtained in this study allowed establishing that factors such as dose and time can influence transfection efficiency in different degrees and that these complexes did not lead to any lethal effect in the MPS I murine model used. |
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Fraga, MichelleCarvalho, Talita Giacomet deBidone, JulianaSchuh, Roselena SilvestriMatte, Ursula da SilveiraTeixeira, Helder Ferreira2018-02-16T02:29:58Z20171178-2013http://hdl.handle.net/10183/172598001019632Mucopolysaccharidosis type I (MPS I) is an autosomal disease caused by alpha-l-iduronidase (IDUA) deficiency. This study used IDUA knockout mice as a model to evaluate whether parameters such as dose of plasmid and time of treatment could influence the transfection efficiency of complexes formed with PEGylated cationic nanoemulsions and plasmid (pIDUA), which contains the gene that encodes for IDUA. Formulations were composed of medium chain triglycerides, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(amino[polyethylene glycol]-2000), 1,2-dioleoyl-sn-glycero-3-trimethylammonium propane (DOTAP), glycerol, and water and were prepared by the adsorption or encapsulation of preformed pIDUA–DOTAP complexes by high-pressure homogenization. A progressive increase in IDUA expression was observed with an increase in the dose and time of transfection for mice treated with both complexes (adsorbed and encapsulated), especially in the liver. Regardless of the complex administered, a significant increase in IDUA activity was detected in lungs and liver compared with nontreated MPS I when a dose of 60 μg was administered and IDUA activity was measured 7 days postadministration. Tissue sections of major organs showed no presence of cell necrosis, inflammatory infiltrate, or an increase in apoptosis. Furthermore, immunohistochemistry for CD68 showed no difference in the number of macrophage cells in treated and nontreated animals, indicating the absence of inflammatory reaction caused by the treatment. The data set obtained in this study allowed establishing that factors such as dose and time can influence transfection efficiency in different degrees and that these complexes did not lead to any lethal effect in the MPS I murine model used.application/pdfengInternational Journal of Nanomedicine. Manchester. Vol. 12 (Mar. 2017), p. 2061-2067NanotecnologiaNanoemulsõesCationic nanoemulsionsDSPE-PEGMPS IPlasmidpIDUAFactors influencing transfection efficiency of pIDUA/nanoemulsion complexes in a mucopolysaccharidosis type I murine modelEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSORIGINAL001019632.pdf001019632.pdfTexto completo (inglês)application/pdf3124441http://www.lume.ufrgs.br/bitstream/10183/172598/1/001019632.pdfe929902d29cd9e748dd744c2aa0455dcMD51TEXT001019632.pdf.txt001019632.pdf.txtExtracted Texttext/plain28236http://www.lume.ufrgs.br/bitstream/10183/172598/2/001019632.pdf.txta8110c4a2356916086bf33083affdc06MD52THUMBNAIL001019632.pdf.jpg001019632.pdf.jpgGenerated Thumbnailimage/jpeg1972http://www.lume.ufrgs.br/bitstream/10183/172598/3/001019632.pdf.jpgedf0943f060034ef75eaf1ef73a6b97bMD5310183/1725982018-10-26 10:23:15.632oai:www.lume.ufrgs.br:10183/172598Repositório InstitucionalPUBhttps://lume.ufrgs.br/oai/requestlume@ufrgs.bropendoar:2018-10-26T13:23:15Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Factors influencing transfection efficiency of pIDUA/nanoemulsion complexes in a mucopolysaccharidosis type I murine model |
title |
Factors influencing transfection efficiency of pIDUA/nanoemulsion complexes in a mucopolysaccharidosis type I murine model |
spellingShingle |
Factors influencing transfection efficiency of pIDUA/nanoemulsion complexes in a mucopolysaccharidosis type I murine model Fraga, Michelle Nanotecnologia Nanoemulsões Cationic nanoemulsions DSPE-PEG MPS I Plasmid pIDUA |
title_short |
Factors influencing transfection efficiency of pIDUA/nanoemulsion complexes in a mucopolysaccharidosis type I murine model |
title_full |
Factors influencing transfection efficiency of pIDUA/nanoemulsion complexes in a mucopolysaccharidosis type I murine model |
title_fullStr |
Factors influencing transfection efficiency of pIDUA/nanoemulsion complexes in a mucopolysaccharidosis type I murine model |
title_full_unstemmed |
Factors influencing transfection efficiency of pIDUA/nanoemulsion complexes in a mucopolysaccharidosis type I murine model |
title_sort |
Factors influencing transfection efficiency of pIDUA/nanoemulsion complexes in a mucopolysaccharidosis type I murine model |
author |
Fraga, Michelle |
author_facet |
Fraga, Michelle Carvalho, Talita Giacomet de Bidone, Juliana Schuh, Roselena Silvestri Matte, Ursula da Silveira Teixeira, Helder Ferreira |
author_role |
author |
author2 |
Carvalho, Talita Giacomet de Bidone, Juliana Schuh, Roselena Silvestri Matte, Ursula da Silveira Teixeira, Helder Ferreira |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Fraga, Michelle Carvalho, Talita Giacomet de Bidone, Juliana Schuh, Roselena Silvestri Matte, Ursula da Silveira Teixeira, Helder Ferreira |
dc.subject.por.fl_str_mv |
Nanotecnologia Nanoemulsões |
topic |
Nanotecnologia Nanoemulsões Cationic nanoemulsions DSPE-PEG MPS I Plasmid pIDUA |
dc.subject.eng.fl_str_mv |
Cationic nanoemulsions DSPE-PEG MPS I Plasmid pIDUA |
description |
Mucopolysaccharidosis type I (MPS I) is an autosomal disease caused by alpha-l-iduronidase (IDUA) deficiency. This study used IDUA knockout mice as a model to evaluate whether parameters such as dose of plasmid and time of treatment could influence the transfection efficiency of complexes formed with PEGylated cationic nanoemulsions and plasmid (pIDUA), which contains the gene that encodes for IDUA. Formulations were composed of medium chain triglycerides, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(amino[polyethylene glycol]-2000), 1,2-dioleoyl-sn-glycero-3-trimethylammonium propane (DOTAP), glycerol, and water and were prepared by the adsorption or encapsulation of preformed pIDUA–DOTAP complexes by high-pressure homogenization. A progressive increase in IDUA expression was observed with an increase in the dose and time of transfection for mice treated with both complexes (adsorbed and encapsulated), especially in the liver. Regardless of the complex administered, a significant increase in IDUA activity was detected in lungs and liver compared with nontreated MPS I when a dose of 60 μg was administered and IDUA activity was measured 7 days postadministration. Tissue sections of major organs showed no presence of cell necrosis, inflammatory infiltrate, or an increase in apoptosis. Furthermore, immunohistochemistry for CD68 showed no difference in the number of macrophage cells in treated and nontreated animals, indicating the absence of inflammatory reaction caused by the treatment. The data set obtained in this study allowed establishing that factors such as dose and time can influence transfection efficiency in different degrees and that these complexes did not lead to any lethal effect in the MPS I murine model used. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017 |
dc.date.accessioned.fl_str_mv |
2018-02-16T02:29:58Z |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/172598 |
dc.identifier.issn.pt_BR.fl_str_mv |
1178-2013 |
dc.identifier.nrb.pt_BR.fl_str_mv |
001019632 |
identifier_str_mv |
1178-2013 001019632 |
url |
http://hdl.handle.net/10183/172598 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
International Journal of Nanomedicine. Manchester. Vol. 12 (Mar. 2017), p. 2061-2067 |
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openAccess |
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