乳铁蛋白修饰水飞蓟素纳米乳的制备及其大鼠体内药代动力学

采用磷脂/吐温80体系制备普通水飞蓟素纳米乳(SM-NE)，通过静电作用在其表面吸附乳铁蛋白得到乳铁蛋白修饰的水飞蓟素纳米乳(LF-SM-NE)，分别考察两者包封率、形态、粒径、Zeta电位，随后采用LC-MS/MS测定经口给药后大鼠体内的吸收情况。研究结果显示，当乳铁蛋白浓度为0.15 mg/mL，温孵时间为4 h时，乳铁蛋白在SM-NE表面的吸附趋于饱和，所得LF-SM-NE外观圆整呈类球状，平均粒径(257±5.9)nm，Zeta电位-(33.1±1.5)mV，包封率为(96.9±1.9)%，载药量为(3.90±0.12)%；与普通水飞蓟素纳米乳相比，经LF修饰后的SM-NE在大鼠体内的药物浓度显著增高，c_max和AUC均提高约2倍左右。因此，经LF修饰后的SM-NE可进一步提高药物的在体内吸收，是一种新型纳米粒口服吸收增强技术，具有良好的应用潜能。

Preparation of lactoferrin-modified silymarin nanoemulsion and its pharmacokinetics in rats

In this paper, silymarin nanoemulsions(SM-NE)were prepared based upon PC/Tween 80 system, and adsorption of lactoferrin(LF)absorbed onto the surface of silymarin nanoemulsions via electrostatic interaction resulted in the formation of lactoferrin-modified silybin nanoemulsions(LF-SM-NE). SM-NE and LF-SM-NE were characterized in terms of the shape, diameter, zeta potential, and entrapment efficiency. In addition, in vivo absorption of SM-NE and LF-SM-NE following oral dosing was investigated by the application of LC-MS/MS in the determination of silymarin in blood sample. The results showed that the saturated adsorption of Lf at the surface of the SM-NE occurred at LF concentration of 0. 15 mg/mL and the incubation time of 4 h. LF-SM-NE were spherical with average particle size of(257±5. 9)nm, zeta potential of -(33. 1±1. 5)mV, entrapment efficiency(96. 9±1. 9)% and drug loading(3. 90±0. 12)%. Compared with those of SM-NE, LF-SM-NE significantly increased drug levels of LF in rats were observed after dosing of LF-SM-NE, and both of c_max and AUC were increased by approximately 2-fold. In summary, LF-SM-NE could improve oral drug absorption of LF in rats. The approach of enhancement in oral absorption of the nanoemulsions shows a promise for the application.