Preparation and in vitro-in vivo evaluation of teniposide nanosuspensions.

Abstract Teniposide (TEN) is a potent, broad spectrum antitumor agent, especially for cerebroma. But the application in clinic was limited because of its poor solubility. In this paper, teniposide nanosuspensions drug delivery system (TEN-NSDDS) for intravenous administration was developed for the first time. Specifically, TEN nanosuspensions were prepared by an anti-solvent sonication–precipitation method and evaluated in comparison with teniposide injection (VUMON) in vitro and in vivo . TEN nanosuspensions prepared showed rod-like morphology and the size was 151 ± 11 nm with a narrow poly dispersion index 0.138 determined by dynamic light scattering. The obtained TEN nanosuspensions were physically stable at least 10 days at 4 °C. And the freeze-drying preparations were stable during 3 months. The cytotoxicity of TEN nanosuspensions were considerable to that of VUMON against U87MG and C6 cells in vitro . When tested in rats bearing C6 tumors, the TEN concentration in the tumors treated by the nanosuspensions was more than 20 times than that by the TEN solution at 2 h. The TEN nanosuspensions exhibited significant tumor growth inhibition. Overall, the results suggested that nanosuspensions was an alternative formulation for teniposide to be administered intravenously, and it would be a promising formulation in clinic.