Dados do Trabalho

Name: Next Frontiers to Cure Cancer
Start: 2023-09-15
End: 2023-09-16
Location: Expo Center Norte (Pavilhão Amarelo)

Título

In vitro cytotoxicity assessment of nanostructured lipid carriers containing fenretinide and perillyl alcohol in breast cancer cells

Introdução

The combination of drugs in pharmacological therapy for cancer is a key strategy against resistance. Fenretinide (Fen) and perillyl alcohol (POH) are promising drugs for breast cancer preventive therapy. However, their adverse effects and low oral bioavailability restrict their systemic use. Co-encapsulation of these drugs in a lipidic delivery system could allow local administration to the mammary tissue, thus enhancing drug concentration in the target tissue while limiting systemic exposure.

Objetivo

Our objective in this work was to develop nanostructured lipid carriers (NLCs) for co-encapsulation and sustained release of Fen and POH, for subcutaneous administration in the breast, aiming at breast cancer chemoprevention, as well as to evaluate their cellular effects on breast cancer cells.

Métodos

First, we determined ratios between fen and POH for potentiation of cytotoxicity. These compounds were combined in proportions of 1:0, 1:1, 1:2 and 1:4 (w/w), which were employed for treatment of MCF-7 and MDA-MB-231 breast cancer cells using the MTT assay. Subsequently, Fen (0.5%) and POH (1%) were encapsulated in NLCs, and the nanocarrier was characterized for size and PdI (through dynamic light scattering) and zeta potential (through electrophoretic light scattering). Drug encapsulation was assessed using ultrafiltration and HPLC for quantification. The nanocarrier influence of drug cytotoxicity was assessed using the MTT assay, using the unloaded NLC and drug solutions as controls.

Resultados

The combination of Fen with POH reduced by more than 2-fold its IC50 in both cell lineages used, but increasing POH more than 2-fold did not further increase the cytotoxicity significantly; therefore, we selected the 1:1 and 1:2 Fen:POH ratios for encapsulation. The size, PdI and zeta potential of the unloaded NLC were 291.8 ± 13.8 nm, 0.204 ± 0.034 and -20.9 ± 2.7 mV, respectively. Fen and POH in concentrations up to 0.5 and 1%, respectively, did not significantly alter these parameters, but Fen at 1% increased size and PdI to 402.3 ± 57.4 and 0.353 ± 0.018, respectively. The NLC containing Fen at 0.5% presented higher IC50 compared to a Fen solution (~2-fold). However, when Fen was co-encapsulated with POH in the NLC, a similar IC50 to the drug solution was observed despite a slower drug release from the NLC. Furthermore, the NLC containing POH and Fen at 0.5% and 1% presented similar IC50 values. The unloaded NLC was cytotoxic only at high concentrations (7,4-18,9 mg/mL).

Conclusões

We observed a potentiation of Fen cytotoxicity when it was combined with POH in breast cancer cells, which has not yet been described to the best of our knowledge. The co-encapsulation with POH enhanced Fen cytotoxicity but increasing Fen concentration from 0.5 to 1% did not further reduce IC50 values. These results support the combination of Fen and POH for potentiation of cytotoxicity and show that their co-encapsulation in suitable lipid nanocarriers did not preclude the cytotoxic effects.