Polymeric micelles co-loaded with paclitaxel and histamine as a new strategy to improve conventional chemotherapy for breast cancer.

MELISA N NICOUD; IGNACIO OSPITAL; MONICA TAQUEZ DELGADO; JENNIFER RIEDEL; PEDRO FUENTES; EZEQUIEL BERNABEU; MARCELA A. MORETTON; ROXANA RUBINSTEIN; MARIA J SALGUEIRO; PAOLO LAURETA; DIEGO CHIAPETTA; VANINA A MEDINA

Congreso; LXVII Reunión Anual de la SAIC, Sociedad Argentina de Investigación Clínica; 2022

Breast cancer is now the most commonly diagnosed cancer and the leading cause of cancer death in women worldwide. Triple negative breast cancer (TNBC) is the most aggressive subtype, associated with the worst prognosis. Non-specific chemotherapeutic drug paclitaxel (PTX) is used as the standard regimen, but its poor solubility and several associated adverse effects conditioned its clinical use. The aim of this work was to improve the chemotherapeutic response of PTX by developing new nanomicellars polymeric formulations. Micellar systems were developed with the biocompatible polymer Soluplus® (S), surface decorated with glucose residues (SG) and co-loaded with histamine (HA, 5 mg/mL) and PTX (4 mg/mL). Their physicochemical characterization includes the determination of micellar size and its distribution, zeta potential and physical stability. We evaluated antitumor activity in human MDA-MB-231 and murine 4T1 TNBC cells. Cytotoxicity and apoptotic assays showed that HA-PTX co-loaded micelles exhibited better antitumor activity compared to free PTX and Genexol® (commercial micellar-based PTX-nanoformulation) and single treatments loaded micelles in both cell lines (P