Publicação
In vivo toxicity screening of classic Gemini and Monoolein nanoparticles using zebrafish embryos
| Resumo: | Gene therapy and drug delivery have evolved and gained great importance over the last years as approaches with great potential in the treatment of genetic diseases and targeted drug delivery. However, achieving efficient delivery through an appropriate vector constitutes a major challenge. Cationic liposomes are one of the most versatile non-viral vectors that have been investigated as an alternative to their viral counterparts. In this regard, their safety profile is a key feature for their validation as proficient nanovehicles for drugs or genetic material delivery to targeted cells, tissues and organisms. The ZET assay is the most often used assay to evaluate the potential toxic effects on fish embryo when exposed to xenobiotics and pharmacological compounds. The toxicity test in zebrafish embryos (Danio rerio) - ZET - is a method approved by the OECD (Organization for Economic Co-Operative Development) that has emerged as an intermediate “tool” to cumbersome and technically challenging analysis in cell culture and ethically sensitive studies in rodents. The aim of this project was to assess if different nanoparticles, constituted by mixtures of gemini [cationic surfactants of m-s-m type with different tail (m = 12 or 14) and spacer (s = 2, 5 or 12) sizes] and monoolein [neutral helper lipid], can represent any risk for the organism and its embryonic development. This analysis was supplemented by conventional cytotoxicity tests using reference cell lines. The obtained results suggest that zebrafish embryos constitute an informative and reliable in vivo model to fast-track the toxicity of lipid-based nanoparticles. |
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| Autores principais: | Fernandes, Joana Filipa Ribeiro |
| Assunto: | Ciências Naturais::Ciências Biológicas |
| Ano: | 2015 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Gene therapy and drug delivery have evolved and gained great importance over the last years as approaches with great potential in the treatment of genetic diseases and targeted drug delivery. However, achieving efficient delivery through an appropriate vector constitutes a major challenge. Cationic liposomes are one of the most versatile non-viral vectors that have been investigated as an alternative to their viral counterparts. In this regard, their safety profile is a key feature for their validation as proficient nanovehicles for drugs or genetic material delivery to targeted cells, tissues and organisms. The ZET assay is the most often used assay to evaluate the potential toxic effects on fish embryo when exposed to xenobiotics and pharmacological compounds. The toxicity test in zebrafish embryos (Danio rerio) - ZET - is a method approved by the OECD (Organization for Economic Co-Operative Development) that has emerged as an intermediate “tool” to cumbersome and technically challenging analysis in cell culture and ethically sensitive studies in rodents. The aim of this project was to assess if different nanoparticles, constituted by mixtures of gemini [cationic surfactants of m-s-m type with different tail (m = 12 or 14) and spacer (s = 2, 5 or 12) sizes] and monoolein [neutral helper lipid], can represent any risk for the organism and its embryonic development. This analysis was supplemented by conventional cytotoxicity tests using reference cell lines. The obtained results suggest that zebrafish embryos constitute an informative and reliable in vivo model to fast-track the toxicity of lipid-based nanoparticles. |
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