Paclitaxel mixed nanomicelles decorated with glucose to optimize the chemotherapeutic treatment of glioma.

RIEDEL J.; PIBUEL M.; DIAZ M.; BERNABEU E.; HAJOS S.; ALLO M.; SANTANDER Y.; LOMPARDIA S.; MORETTON M.A.; HOCHT C.; CHIAPPETTA D.A.

Jornada; XX Jornadas anuales de la Sociedad Argentina de Biología.; 2018

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 and spherical morphology with a unimodal size distribution. In addition, nanomicelles remained stable under 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 than the glucose-free system (0.62x10-4±0.09x10-4μg/mL) and PTX solution (2.50x10-4±0.19x10-4μg/mL) for U251 cell line. Particularly, for LN229 cell line, the IC50 values for the drug-loaded MNMs without (1.5x10-4μg/mL) and with (1.8x10-4μg/mL) glucose were similar and 3.4-fold and 2.8-fold lower than PTX solution, respectively. Finally, in vivo results showed that the PTX-loaded MNMs increased more than threefold brain accumulation of the cytotoxic agent compared to a PTX solution in Wistar rats. Overall, our MNMs represent a feasible platform to improve conventional glioma chemotherapy.