Paclitaxel nanosuspensions coated with P-gp inhibitory surfactants: I. Acute toxicity and pharmacokinetics studies

• Paclitaxel nanosuspensions were successfully prepared by evaporative precipitation into aqueous solution (EPAS) method.
• Paclitaxel nanoparticles were rod shape under the transmission electron microscope, and the particle size was 135.4 nm.
• Acute toxicity study showed the LD50 of paclitaxel nanosuspensions is two times more than that of marked injection.
• Paclitaxel nanosuspensions displayed a different pharmacokinetic property compared with the marketed injectable solution.

PurposeThe aim of the present study was to evaluate the acute toxicity and pharmacokinetics of paclitaxel nanosuspensions stabilized with TPGS in mice.MethodThe paclitaxel nanosuspensions were prepared by evaporative precipitation into aqueous solution (EPAS) method, and freeze-dried powders of the nanosuspensions were obtained through lyophilization process. The morphology and particle size of nanosuspensions were determined by transmission electron microscope and Zetasizer, respectively. The acute toxicity and pharmacokinetics of paclitaxel nanosuspensions after intravenous administration to Kunming mice were studied. A marketed paclitaxel injectable solution was studied parallelly.ResultsThe paclitaxel nanoparticles were in rod shape under transmission electron microscope, and their mean particle size was 135.4 ± 5.7 nm. Results of acute toxicity showed the LD50 of paclitaxel nanosuspensions was 98.63 mg/kg, twice more than that of the marketed injection (41.46 mg/kg). After intravenous injection paclitaxel nanosuspensions displayed different pharmacokinetic properties in comparison with the marketed injectable solution, including a decreased initial drug concentration, increased plasma half-life, AUC and MRT.ConclusionsThe paclitaxel nanosuspensions prepared in this study could markedly enhance the tolerance dosage in mice, and manifest different pharmacokinetic properties compared with the solution.

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