دورية أكاديمية
Development, formulation, and cellular mechanism of a lipophilic copper chelator for the treatment of Wilson's disease
| العنوان: | Development, formulation, and cellular mechanism of a lipophilic copper chelator for the treatment of Wilson's disease |
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| المؤلفون: | Gauthier, Laura, Charbonnier, Peggy, Chevallet, Mireille, Delangle, Pascale, Texier, Isabelle, Gateau, Christelle, Deniaud, Aurélien |
| المساهمون: | Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Département Microtechnologies pour la Biologie et la Santé (DTBS), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Département Interfaces pour l'énergie, la Santé et l'Environnement (DIESE), Métaux et Organes (MET&OR), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Labex Arcane, ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017) |
| المصدر: | ISSN: 0378-5173 ; International Journal of Pharmaceutics ; https://hal.science/hal-03455339Test ; International Journal of Pharmaceutics, 2021, 609, pp.121193. ⟨10.1016/j.ijpharm.2021.121193⟩. |
| بيانات النشر: | HAL CCSD Elsevier |
| سنة النشر: | 2021 |
| المجموعة: | Université Grenoble Alpes: HAL |
| مصطلحات موضوعية: | Hepatocytes, Copper chelator, Nanolipid formulation, Wilson's disease, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [CHIM.COOR]Chemical Sciences/Coordination chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism |
| الوصف: | International audience ; Copper homeostasis is finely regulated in human to avoid any detrimental impact of free intracellular copper ions. Upon copper accumulation, biliary excretion is triggered in liver thanks to trafficking of the ATP7B copper transporter to bile canaliculi. However, in Wilson's disease this protein is mutated leading to copper accumulation. Current therapy uses Cu chelators acting extracellularly and requiring a life-long treatment with side effects. Herein, a new Cu(I) pro-chelator was encapsulated in long-term stable nanostructured lipid carriers. Cellular assays revealed that the pro-chelator protects hepatocytes against Cu-induced cell death. Besides, the cellular stresses induced by moderate copper concentrations, including protein unfolding, are counteracted by the pro-chelator. These data showed the pro-chelator efficiency to deliver intracellularly an active chelator that copes with copper stress and surpasses current and under development chelators. Although its biological activity is more mitigated, the pro-chelator nanolipid formulation led to promising results. This innovative approach is of outmost importance in the quest of better treatments for Wilson's disease. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-03455339; https://hal.science/hal-03455339Test; https://hal.science/hal-03455339/documentTest; https://hal.science/hal-03455339/file/Gauthier-Int-J-Pharmaceutics-v-finale-auteurs.pdfTest |
| DOI: | 10.1016/j.ijpharm.2021.121193 |
| الإتاحة: | https://doi.org/10.1016/j.ijpharm.2021.121193Test https://hal.science/hal-03455339Test https://hal.science/hal-03455339/documentTest https://hal.science/hal-03455339/file/Gauthier-Int-J-Pharmaceutics-v-finale-auteurs.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.720D7600 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.ijpharm.2021.121193 |
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