Paclitaxel mixed nanomicelles: an interesting platform to optimize chemotherapeutic treatment of glioma.

RIEDEL, JENNIFER; BERNABEU, EZEQUIEL; LOMPARDÍA, SILVINA LAURA; PIBUEL, MATÍAS; HAJOS, SILVIA; MARCELA MORETTON; DÍAZ, MARIÁNGELES; HÖCHT, CHRISTIAN; DIEGO A. CHIAPPETTA

Buenos Aires

Congreso; IV International Congress in Translational Medicine; 2018

IMBS

Paclitaxel mixed nanomicelles: an interesting platform to optimizechemotherapeutic treatment of gliomaRiedel, Jennifer 1; Pibuel, Matías 3,4; Díaz, Mariángeles 3,4; Bernabeu,Ezequiel 1,4; Hajos, Silvia 3,4; Höcht, Christian 2; Lompardía, Silvina Laura 3,4;Marcela Moretton 1,4; Diego A. Chiappetta 1,41 Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica,Departamento de Tecnología Farmacéutica.2 Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica,Departamento de Farmacología.3 Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica-IDEHU,UBA-CONICET.4 Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)According to the World Health Organization, cancer is the second cause of deathafter cardiovascular diseases. Most cancers correspond to solid tumors, beingbrain tumors (gliomas) the ones with worst prognosis. Unfortunately, thechemotherapy is very limited due to the poor penetration of the drugs through theblood brain barrier (BBB) and the poor targeting of them towards the tumor cells.Further, the practical application of paclitaxel (PTX), one of the most effectiveantineoplastic drugs, is limited by its poor aqueous solubility (0.3-0.5μg/mL) andpoor penetration across the BBB. Therefore, it is critical to develop novel nanovehiclesto 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 andcellular uptake in breast (MCF-7, MDA-MB-231) cancer cell lines vs their glucosefreecounterparts [1].In this framework, Soluplus®:TPGS MNMs appear as an attractivenanotechnological approach to optimize glioma chemotherapy. Hence, the maingoal 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 reachthis objective we prepare MNMs employing a glycosylated derivative of Soluplus®(Solu-Glu) and TPGS (weight ratio 5:1%w/v) using a clinically relevant PTXconcentration (4mg/mL). In this context, the surface decoration of the nanocarrierwith glucose could promote an active PTX targeting to brain cancer cells lines(U251 and LN229) since glucose transporters are overexpressed in the endothelialcells of the BBB and in the glioma cells. First, we synthesized Solu-Glu by meansof ring opening reaction of δ-gluconolactone as previously reported [1]. Then, PTXloadedSolu-Glu:TPGS MNMs were obtained, characterized and their in vitrocytotoxicity performance was evaluated in both glioma cells lines using XTT assay.PTX-loaded Solu-Glu:TPGS MNMs and their glucose-free counterparts presenteddiameter hydrodynamic values between 100 and 120nm. The morphologicalcharacterization employing transmission electronic microscopy of these MNMsdemonstrated rod-shape micelles with a unimodal size distribution. Finally, theIC50 value for the PTX-loaded MNMs with glucose (0.13x10-4±0.03x10-4μg/mL)was significantly lower (p