GLISONI Romina Julieta
congresos y reuniones científicas
Novel anticancer fluorophenazine within nanomicelles: Synthesis, phisicochemical characterization and in vitro evaluation of the antitumor effectiveness.
LECOT N.; ODDONE N.; CABRAL P.; GLISONI RJ.; CERECETTO H.; GONZALEZ M.
Mar del Plata, Argentina
Congreso; Reunión Conjunta 2016 SAIC-SAI-SAFE NANOMED-AR; 2016
The breast cancer is the most frequent in women, with an increase in developing countries mainly because the diagnosis is made at late stages. Breast cancer is a solid tumor that is characterized by a high degree of hypoxic zones. We recently discovered a new derivative of phenazine (FNZ; N5,N10-dioxide of 2-amino-7(8)-fluorophenazine), that acts as a selective agent in hypoxic conditions, regarded as a lead in treating solid tumors. To enhance FNZ-tumor disposition and penetration into inner tumor regions and concurrently prolong overall circulation time to favor the accumulation in tumor tissue via enhanced permeation and retencion effect (EPR effect), we proposed its vehiculization into polymeric nanomicelles (PMs), based of PEO-PPO copolymers. The encapsulation efficiency (EE) and the physicochemical characterization of FNZ-loaded nanomicelles (T1307-FNZ, F127-FNZ and T1307:F127-FNZ) were evaluated in order to define reproducibility in terms of in vitro parameters. PMs (10% w/v) increased the solubility of FNZ in 3-4 times (EE=52-78%) with an improved stability for the mixed ones (T1307:F127). The nanosystems were characterized for the particle size (two marked populations with 7-8 and 40-45 nm with narrow size distribution) and Zeta potential (-4 mV) determined by dynamic light scattering (DLS). On the other hand, free-FNZ and FNZ-loaded PMs were evaluated in their capability to inhibit in vitro 4T1 murine mammary tumor cells. The cell viability assay was performed using the MTT methodology (48h). FNZ showed antitumor efficacy at concentration higher than 20uM. The new systems, i.e. T1307-FNZ, F127-FNZ and T1307:F127-FNZ, displayed better in vitro behavior. Finally, more extensive studies on the antitumor effectiveness of FNZ-loaded polymeric nanocarriers are required, these preliminary results indicate that these PEO-PPO nanomicelles and loaded with FNZ are potential candidates as therapeutic agents in breast cancer treatment.