Paclitaxel loaded nanoparticles of biodegradable polymers for cancer chemotherapy

Abstract

Paclitaxel, one of the best antineoplastic agents, exhibits excellent anti-proliferative activity against a wide spectrum of cancers. This research aims to develop an effective formulation of paclitaxel to improve its therapeutic index and to reduce the adverse effects of adjuvant Cremophor EL in its current sole clinical formulation (TaxolA?). Nanoparticles of biodegradable polymers could provide an ideal solution for the alternative formulation devoid of CrEL, which also provide a sustained and controlled delivery of the drug and with further development, promote oral chemotherapy. In our nanoparticle technique, vitamin E TPGS is used as a necessary auxiliary in nanoparticle formulation as well as a a??maska?? for the nanoparticles to cross the GI barrier for oral chemotherapy. Paclitaxel-loaded, TPGS-emulsified poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by a modified solvent extraction/evaporation technique. Nanoparticles of various recipes were characterized by various state-of-the-art techniques. Caco-2 and HT-29 cells were employed as a model GI barrier for oral bioavailability. Cellular uptake of nanoparticle was found strongly dependent on the size and surface coating of nanoparticles. In vitro cytotoxicity of the nanoparticle formulation was assessed and in vivo pharmacokinetics was measured, in close comparison with TaxolA?. Both in vitro and in vivo evaluations showed advantages of the nanoparticle formulation over TaxolA?.