HISTAMINE COMBINED STRATEGIES TO IMPROVE THE THERAPEUTIC EFFICACY OF PACLITAXEL IN TRIPLE NEGATIVE BREAST CANCER

NICOUD, MELISA B; OSPITAL, IGNACIO A.; TÁQUEZ DELGADO, MÓNICA A.; RIEDEL, JENNIFER; FUENTES, PEDRO; BERNABEU, EZEQUIEL; MORETTON, MARCELA A.; SALGUEIRO, MARÍA J.; CHIAPPETTA, DIEGO A.; MEDINA, VANINA A

Congreso; LXVI Reunión Anual de la SAIC, Sociedad Argentina de Investigación Clínica; 2021

Sociedad Argentina de Investigación Clínica

Breast cancer is the most frequently diagnosed neoplasia and aleading cause of cancer related death in women worldwide. Triplenegative breast cancer (TNBC) is an aggressive subtype, associatedwith poor prognosis. The standard treatment regimen for TNBC isbased on the administration of highly toxic chemotherapeutic drugs(anthracyclines/taxanes). Paclitaxel (PTX) is a first-line therapy forTNBC and has low water solubility, poor permeability, and producessevere adverse effects, which limit its clinical use. The aim of thiswork was to improve the therapeutic index of PTX through the designof combined strategies. For that purpose, we developed nanomicellarpolymeric formulations of Soluplus® (S) and Soluplus® surfacedecorated with glucose residues (SG) co-loaded with histamine(HA, 5 mg/mL) and PTX (4 mg/mL). The micellar size, evaluated bydynamic light scattering, showed a hydrodynamic diameter between80 and 100 nm for loaded nanoformulations with a unimodal sizedistribution. Cytotoxicity and apoptosis assays were performed toassess their efficacy in vitro in human MDA-MB-231 and murine 4T1TNBC cells. Results showed that histamine improved the antitumoralactivity of free PTX and Genexol® (commercial micellar-basedPTX- nanoformulation) at low concentrations (0.01-0.1 uM) in bothcell lines (P