Anticancer properties of lipid and poly(ε-caprolactone) nanocapsules loaded with ferrocenyl-tamoxifen derivatives
In: Journal of Pharmacy and Pharmacology, Jg. 70 (2018-08-23), S. 1474-1484
Online
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Zugriff:
Objective We synthesized new tamoxifen derivatives as anticancer drug candidates and elaborated on convection-enhanced delivery (CED) as a strategy for delivery. Methods To 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 findings Starting 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. Conclusions Phthalimido- 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: | Sancey, Lucie ; Busser, Benoit ; Pezet, Mylène ; Gibaud, Stéphane ; Rhouma, Ali ; Jaouen, Gérard ; Pigeon, Pascal ; Marrakchi, Naziha ; Aroui, Sonia ; Najlaoui, Feten ; Michel De Waard ; 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) ; Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris) ; Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris) ; Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Sorbonne Université (SU)-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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Sorbonne Université (SU)-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 [Grenoble] (CHU)-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 ; unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX) ; Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE) ; Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
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Zeitschrift: | Journal of Pharmacy and Pharmacology, Jg. 70 (2018-08-23), S. 1474-1484 |
Veröffentlichung: | Oxford University Press (OUP), 2018 |
Medientyp: | unknown |
ISSN: | 2042-7158 (print) ; 0022-3573 (print) |
DOI: | 10.1111/jphp.12998 |
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