Anticancer properties of lipid and poly(ε-caprolactone) nanocapsules loaded with ferrocenyl-tamoxifen derivatives.
J Pharm Pharmacol
; 70(11): 1474-1484, 2018 Nov.
Article
em En
| MEDLINE
| ID: mdl-30141195
ABSTRACT
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. KEYFINDINGS:
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Poliésteres
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Tamoxifeno
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Neoplasias Encefálicas
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Neoplasias da Mama
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Portadores de Fármacos
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Glioblastoma
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Nanocápsulas
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Lipídeos
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Antineoplásicos
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article