Anticancer properties of lipid and poly(ε-caprolactone) nanocapsules loaded with ferrocenyl-tamoxifen derivatives
In: ISSN: 0022-3573 ; Journal of Pharmacy and Pharmacology ; https://hal.science/hal-01861749 ; Journal of Pharmacy and Pharmacology, 2018, 70 (11), pp.1474-1484. ⟨10.1111/jphp.12998⟩ ; https://onlinelibrary.wiley.com/doi/abs/10.1111/jphp.12998, 2018
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Zugriff:
International audience ; ObjectiveWe synthesized new tamoxifen derivatives as anticancer drug candidates and elaborated on convection‐enhanced delivery (CED) as a strategy for delivery.MethodsTo overcome the issue of their poor solubility, these ferrocenyl‐tamoxifen derivatives were esterified and encapsulated into different nanocarriers, that is lipid (LNC) and polymeric nanocapsules (PNL‐NC). We describe the chemistry, the encapsulation and the physicochemical characterization of these formulations.Key findingsStarting compounds [phthalimido‐ferrocidiphenol and succinimido‐ferrocidiphenol], esterified prodrugs and their nanocapsules formulations were characterized.These drug candidates displayed a strong in vitro activity against breast and glioblastoma cancer cells. The ester prodrugs were toxic for glioblastoma cells (IC50 = 9.2 × 10−2 μm and 6.7 × 10−2 μm, respectively). The IC50 values for breast cancer cells were higher for these compounds. The encapsulation of the esterified compounds in LNCs (≈50 nm) or PCL‐NCs (≈300 nm) did not prevent their efficacy on glioblastoma cells. These anticancer effects were due to both blockade in the S‐phase of the cell cycle and apoptosis. Moreover, the tamoxifen derivatives‐loaded nanocapsules induced no toxicity for healthy astrocytes and showed no haemolytic properties. Loaded Lipid Nanocapsules (LNCs) presented interesting profiles for the optimal delivery of active compounds.ConclusionsPhthalimido‐ and Succinimido‐esters represent an innovative approach to treat cancers with cerebral localizations such as glioblastoma or brain metastases from breast cancers.
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Anticancer properties of lipid and poly(ε-caprolactone) nanocapsules loaded with ferrocenyl-tamoxifen derivatives
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Autor/in / Beteiligte Person: | Najlaoui, Feten ; Pigeon, Pascal ; Aroui, Sonia ; Pezet, Mylène ; Sancey, Lucie ; Marrakchi, Naziha ; Rhouma, Ali ; Jaouen, Gérard ; de Waard, Michel ; Busser, Benoît ; Gibaud, Stéphane ; Laboratoire des Venins et Toxines, Institut Pasteur de Tunis ; Institut Pasteur de Tunis ; Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP) ; Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR) ; Université de Lorraine (UL) ; Institut Parisien de Chimie Moléculaire (IPCM) ; Chimie Moléculaire de Paris Centre (FR 2769) ; École normale supérieure - Paris (ENS-PSL) ; Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP) ; Université Paris Sciences et Lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris) ; Université Paris Sciences et Lettres (PSL)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL) ; Université Paris Sciences et Lettres (PSL)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) ; Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP) ; Université Paris Sciences et Lettres (PSL) ; Chemical Biology (CHEMBIO) ; Université Paris Sciences et Lettres (PSL)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769) ; Université de Monastir - University of Monastir (UM) ; Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB) ; Centre Hospitalier Universitaire CHU Grenoble (CHUGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes 2016-2019 (UGA 2016-2019 ) ; Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules (LR11IPT08) ; Olive Tree Institute ; ITX - unité de recherche de l'institut du thorax (ITX) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE) ; Université de Nantes (UN)-Université de Nantes (UN) |
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Zeitschrift: | ISSN: 0022-3573 ; Journal of Pharmacy and Pharmacology ; https://hal.science/hal-01861749 ; Journal of Pharmacy and Pharmacology, 2018, 70 (11), pp.1474-1484. ⟨10.1111/jphp.12998⟩ ; https://onlinelibrary.wiley.com/doi/abs/10.1111/jphp.12998, 2018 |
Veröffentlichung: | HAL CCSD ; Royal Pharmaceutical Society of Great Britain, 2018 |
Medientyp: | academicJournal |
DOI: | 10.1111/jphp.12998 |
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