PACLITAXEL MIXED NANOMICELLES DECORATED WITH GLUCOSE TO OPTIMIZE THE CHEMOTHERAPEUTIC TREATMENT OF GLIOMA

DÍAZ M.; ALLO M.; MORETTON M.; RIEDEL J.; BERNABEU E. ; SANTANDER Y; HÖCHT C.; PIBUEL M.; HAJOS S. E. ; LOMPARDÍA S. L. ; CHIAPPETTA D.

Congreso; Reunión Conjunta SAB-SUB; 2018

SAB-SUB

According to the WHO, cancer is the second cause of death after cardiovascular diseases. Most cancers correspond to solid tumors, being brain tumors (gliomas) the ones with worst prognosis. Unfortunately, the chemotherapy is very limited due to the poor penetration of the drugs through the blood brain barrier (BBB) and the poor targeting of them towards the tumor cells. Paclitaxel (PTX) is one of the most effective antineoplastic drugs against a wide spectrum of malignant tumors, including glioma. However, the most used formulation (Taxol®) produces serious adverse effects and its clinical application in glioma is limited due to the poor penetration of the drug into the central nervous system (CNS). Therefore, it is critical to develop novel nano-vehicles to improve the penetration across the BBB and the therapeutic efficiency of PTX. Recently, we have prepared PTX-loaded Soluplus®:TPGS mixed nanomicelles (MNMs) surface decorated with glucose in order to optimize the treatment of glioma since glucose transporters are overexpressed in the endothelial cells of the BBB and in the glioma cells. PTX-loaded MNMs with glucose and their glucose-free counterparts presented diameter hydrodynamic values between 100-140 nm with a unimodal size distribution and spherical morphology employing transmission electronic microscopy. Also, neutral zeta potential values were observed. In addition, nanomicelles remained stable under 1/100 dilution in different simulated biological fluids presenting a constant size ratio during 24 hours at 37°C. Regards to in vitro cytotoxicity in glioma cell lines, the IC50 value for the MNMs-PTX-glucose (0.13x10-4±0.03x10-4μg/mL) was significantly lower (p