Anticancer properties of lipid and poly(ε-caprolactone) nanocapsules loaded with ferrocenyl-tamoxifen derivatives

• Published in: Journal of pharmacy and pharmacology Vol. 70; no. 11; p. 1474
• Main Authors: Najlaoui, Feten, Pigeon, Pascal, Aroui, Sonia, Pezet, Mylène, Sancey, Lucie, Marrakchi, Naziha, Rhouma, Ali, Jaouen, Gérard, De Waard, Michel, Busser, Benoit, Gibaud, Stéphane
• Format: Journal Article
• Language: English
• Published: England 01.11.2018
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Apoptosis - drug effects; Brain Neoplasms - drug therapy; Brain Neoplasms - pathology; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Chemistry, Pharmaceutical - methods; Drug Carriers; Drug Compounding; Drug Liberation; Female; Glioblastoma - drug therapy; Glioblastoma - pathology; Humans; Kinetics; Lipids - chemistry; Male; Nanocapsules; Polyesters - chemistry; Rats, Inbred F344; Solubility; Tamoxifen - analogs & derivatives; Tamoxifen - chemical synthesis; Tamoxifen - pharmacology; ferrocenyl-tamoxifen derivatives; breast cancer; polymer nanocapsules; glioblastoma; Lipid nanocapsules
• DOI: 10.1111/jphp.12998

We synthesized new tamoxifen derivatives as anticancer drug candidates and elaborated on convection-enhanced delivery (CED) as a strategy for delivery. 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. 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 (IC = 9.2 × 10 μm and 6.7 × 10 μm, respectively). The IC 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. Phthalimido- and Succinimido-esters represent an innovative approach to treat cancers with cerebral localizations such as glioblastoma or brain metastases from breast cancers.