Improved in vitro cytotoxicity and cellular uptake of paclitaxel loaded nanoparticles made of TPGS-PCL versus mPEG-PCL and Abraxane®

BERNABEU E; MORETTON M; LEGASPI M; GONZÁLEZ L; BERNABEU E, HELGUERA G, LEGASPI MJ, GONZALEZ L, HOCHT C, TAIRA C, CHIAPPETTA DA.

Córdoba

Congreso; RICIFA 2014. 3º Reunión Internacional de Ciencias Farmacéuticas.; 2014

Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba. Departamento de Farmacia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario

Paclitaxel (PTX) is an antineoplastic drug used to treat multiples cancers types. Because PTX has very low aqueous solubility, the conventional market formulation contains high concentration of Cremophor-EL® (CrEL) which is associated with a great number of side effects. Polymeric NPs may provide an alternative to the use of toxic excipients improving solubility and favoring a controlled release of chemotherapeutic drugs. Modification of NPs with polyethylene glycol (PEG) is the most widely used method to reduce the clearance of NPs from the circulation. However, PEGylation strongly inhibits cellular uptake which can negatively influence the NPs performance as drug carrier. D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) is a water-soluble form of vitamin E. NPs surface modifications with TPGS, increase system stability in biological fluids. In additton, TPGS is selectively Cytotoxic to cancer cells so could be used for the delivery of anticancer drugs. In this sense, we have synthesized TPGSpoly(ε-caprolactone) (TPGS-PCL) and methoxy PEG-poly(ε-caprolactone) (mPEGPCL) copolymers with the same hydrophobic?hydrophilic balance. TPGS-PCL and mPEG-PCL NPs were prepared by emulsion-solvent evaporation technique with a size value of 240 and 300 nm, respectively. The in vitro PTX release was slow and continuous from both NPs. Cellular uptake and in vitro anti-tumoral activity was assessed using two human breast cancer cell lines (MCF-7 and MDA-MB-231). PTXloaded TPGS-PCL NPs exhibited better anti-cancer activity compared to PTX solution, PTX-loaded mPEG-PCL NPs and Abraxane®. The IC50 value for PTX-loaded PCLTPGS NPs was 4 and 3.2 times lower than mPEG-PCL NPs after 72 h of incubation for MCF-7 and MDA-MB-231 cell lines, respectively. PCL-TPGS NPs exhibited an increased in cellular uptake for both cancer cells in comparison with the mPEG-PCL NPs. In conclusion, the novel NPs investigated might be an alternative nanotechnological platform for PTX delivery system in cancer chemotherapy.