NOVEL GLYCOSYLATED SOLUPLUS: TPGS MIXED MICELLES FOR PACLITAXEL ACTIVE TARGETING TO BREAST CANCER CELLS

MORETTON MARCELA; GROTZ ESTEFANIA; CAGEL MAXIMILIANO; CHIAPPETTA DIEGO A.; BERNABEU EZEQUIEL; GONZALEZ LORENA

Rosario

Otro; 4ta. Reunión Internacional de Ciencias Farmacéuticas; 2016

Cancer remains a leading cause of death worldwide according to the World Health Organization. Breast cancer is the top cancer in women where paclitaxel (PTX) represents one of the most effective antineoplastic drugs. It is a poorly-water soluble drug (0.3-0.5 μg/mL) commercially formulated as Taxol®. Previously, we developed a novel Soluplus:TPGS (weight ratio 4:1 %w/v) mixed nanomicelles (NMs) employing a clinically relevant PTX concentration (4 mg/mL), aiming to avoid Taxol® main side effects. Further we aim to surface decorate the nanocarrier with glucose to promote an active PTX targeting to a breast cancer cell line (MCF-7). First, we synthesized a glycopolymer by means of ring opening polymerization of δ-gluconolactone initiated by Soluplus. The derivative obtained Soluplus(Glu) was characterized by proton nuclear magnetic resonance. The hydrodynamic diameter of Soluplus(Glu) NMs was characterized by dynamic light scattering (100.3±3.8 nm) as well as the critical micellar concentration value (0.0151 %w/v). Further, an agglutination assay employing a carbohydrate-binding lectin (Concanavalin A) was performed to characterize the NMs surface decoration. Micellar agglutination was observed by transmission electronic microscopy only for the NMs with glucose. Then, PTX-loaded (4 mg/mL) mixed NMs using Soluplus(Glu), Soluplus and TPGS (weight ratio 1:3:1 %w/v) (Soluplus(Glu):TPGS) were obtained and their in vitro cytotoxicity performance was evaluated in MCF-7. Results were compared with those observed for PTX-loaded (4 mg/mL) Soluplus:TPGS NMs and Genexol® (a novel micellar-based PTX formulation). The IC50 value for the NMs with glucose (6.07±0.28 μg/mL) was significantly lower (P