Nanomicellar formulation of paclitaxel and histamine as a potential breast cancer chemotherapeutic system

TÁQUEZ DELGADO; BERNABEU E.; SALGUEIRO, JIMENA; NICOUD, MELISA B.; FUENTES, P; RUBINSTEIN R; MEDINA, VANINA A.; RIEDEL JENNIFER; MORETTON M.; CHIAPPETTA D.A.

hannover

Encuentro; European Histamine Research Society 50th Annual Meeting; 2022

Breast cancer is the most frequently diagnosed neoplasia and a leading cause of cancer related death in women worldwide. Triple negative breast cancer (TNBC) is an aggressive subtype, associated with poor prognosis. Paclitaxel (PTX) is a first-line therapy for TNBC and has low water solubility, poor permeability, and produces severe adverse effects, which limit its clinical use. The aim of this work was to improve the therapeutic index of PTX through the design of combined strategies. For that purpose, we developed nanomicellar polymeric formulations of Soluplus® (S) surface decorated with glucose residues (SG) co-loaded with histamine (HA, 5 mg/mL) and PTX (4 mg/mL). The micellar size, evaluated by dynamic light scattering, showed a hydrodynamic diameter between 80 and 100 nm for loaded nanoformulations with a unimodal size distribution. Cytotoxicity and apoptosis assays were performed to assess their efficacy in vitro in human MDA-MB-231 and murine 4T1 TNBC cells. Results showed that histamine improved the antitumoral activity of free PTX and Genexol® (commercial micellar-based PTX-nanoformulation) at low concentrations (0.01-0.1 uM) in both cell lines (P