According to the World Health Organization, 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. Further, the practical application of paclitaxel (PTX), one of the most effective antineoplastic drugs, is limited by its poor aqueous solubility (0.3-0.5μg/mL) and poor penetration across the BBB. Therefore, it is critical to develop novel nano-vehicles to improve the aqueous solubility and the therapeutic efficiency of PTX. Recently, we have reported that PTX-loaded Soluplus®:TPGS mixed nanomicelles (MNMs) surface decorated with glucose enhanced the in vitro citotoxicity and cellular uptake in breast (MCF-7, MDA-MB-231) cancer cell lines vs their glucose-free counterparts [1]. In this
framework, Soluplus®:TPGS MNMs appear as an attractive nanotechnological approach to optimize glioma chemotherapy. Hence, the main goal of our investigation is the improvement of the PTX uptake by glioma cells, representing an enhancement of the in vitro citotoxicity vs a PTX solution. To reach this objective we prepare MNMs employing a glycosylated derivative of Soluplus® (Solu-Glu) and TPGS (weight ratio 5:1%w/v) using a clinically relevant PTX concentration (4mg/mL). In this context, the surface decoration of the nanocarrier with glucose could promote an active PTX targeting to brain cancer cells lines (U251 and LN229) since glucose transporters are overexpressed in the endothelial cells of the BBB and in the glioma cells. First, we synthesized Solu-Glu by means of ring opening reaction of δ-gluconolactone as previously reported [1]. Then, PTX-loaded Solu- Glu:TPGS MNMs were obtained, characterized and their in vitro cytotoxicity performance was evaluated in both glioma cells lines using XTT assay. PTX-loaded Solu-Glu:TPGS MNMs and their glucose-free counterparts presented diameter hydrodynamic values between 100 and 120nm. The morphological characterization employing transmission electronic microscopy of these MNMs demonstrated rodshape micelles with a unimodal size distribution. Finally, the IC50 value for the PTXloaded MNMs with glucose (0.13x10-4±0.03x10-4μg/mL) was significantly lower (p<0.05) 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) Glu were similar and 3.4-fold and 2.8-fold lower than PTX solution, respectively (p<0.05). Overall, our MNMs represent a feasible platform to improve conventional glioma chemotherapy. Future studies will be focused on the in vivo penetration of these nanocarriers to the SNC. [1] Moretton et al. Eur.J.Pharm.Biopharm.2017May;114:305-316.