ABSTRACT
Objective: To investigate the cytotoxicity of paclitaxel nanocrystals on breast cancer cells and the characteristics of pharmacokinetics and tissue distribution in mice. Methods: Precipitation method was used to prepare paclitaxel nanocrystals. Particle size, Zeta potential and particle morphology of nanocrystals were determined by dynamic light scattering and the transmission electron microscopy. MTT assay was performed to evaluate the cytotoxicity of nanocrystals on breast cancer cells. Paclitaxel concentration in vivo was detected by LC-MS/MS. Results: The average particle size of paclitaxel nanocrystals was 194.9 nm and the Zeta potential value was -29.6 mV. There was no significant difference (P >0.05) between paclitaxel nanocrystals and commercial Taxol on the cytotoxicity against MCF-7 cells. The plasma concentration-time profiles of paclitaxel nanocrystals and Taxol in mice were described by a two-compartment model. The t1/2,α were (2.91 ± 0.067) and (3.70 ± 0.063) min, t1/2, β were (69.41 ± 0.73) and (53.94 ± 0.62) min, AUC(0-∞) were (276 700 ± 960) and (464 160 ±710) μg · min/L, CL were (0. 036 ± 0. 011) and (0. 022 ± 0. 010) L/(min · kg), respectively. The drug concentration in liver and spleen was significantly increased for paclitaxel nanocrystals compared with Taxol(P<0.01), but lower in heart and kidneys(P < 0.01). Conclusion: Paclitaxel nanocrystals have the same cytoxicity as Taxol. Paclitaxel nanocrystals, mainly absorbed by the liver and spleen, could rapidly distribute into the surrounding tissue and reduce the toxicity in heart and kidneys, which have clinical significance to decrease the side effects.