Studies On Nanostructured Lipid Carrier Loaded With Docetaxel

The objective of this paper was to prepare nanostrutured lipid carrier loaded with docetaxel （DCT-NLC） by hot high pressure homogenization method and solvent diffusion method, to investigate the physico-chemical characteristics of the nanoparticles, and to study pharmacokinetics as well as tissue distribution in vivo.The partition of oil/water and the apparent solubility of docetaxel in water and lipid oil phase were determined by high-performance liquid chromatography （HPLC） method. Ultra-filtration and dialysis methods were developed to determine the encapsulation efficiency of DCT-NLC.Hot high pressure homogenization method and solvent diffusion method were employed to prepared DCT-NLC. With the criteria of encapsulation efficiency and deposited stability, orthogonal design experiments were performed to optimize the formula and the protocols for the process.In order to improve the drug stability, a freeze-drying method was developed. The physico-chemical characteristics of DCT-NLC were evaluated before and after freeze-drying. The results showed that the mean diameter and zeta potential of DCT-NLC before and after lyophilyzation were 156 nm, 245 nm, -43.6 mv and -38.8 mv for hot high pressure homogenization method; 129 nm, 165 nm, -29.2 mv and -24.1 mv for solvent diffusion method. X-ray diffraction and DSC investigations illustrated that DCT was distributed in nanoparticles in molecule or amorphous status. The cumulated release rates of DCT-NLC prepared by hot high pressure homogenization method and solvent diffusion method were 13.34% and 12.90%, separately. The lyophilized product was stable under room temperature for 3 months.A reliable analysis method by HPLC was established to determine the concentration of DCT in rat plasma. After iv. administration at a single dosage of 10.0mg·kg^-1 in rats, drug concentration in plasma was assayed at different times. The data of experiment were calculated by Statistic Quadrature. The results of the drug pharmacokinetics in vivo showed that the DCT-NLC had a much higher AUC, AUMC, MRT and obviously lower ke and CL than DCT injection.The tissue distribution was studied after iv. administration at a single dosage of 10mg/kg in rats. Compared with DCT injection, DCT-NLC showed obviously higher concentration in spleen, liver and especially in lung, while exhibited lower concentration in heart and kidney, which may decrease drug side effects and improve treatment efficacy.