Research On Preparation And Pharmacokinetics Of Saffower Yellower Niosomes

Safflower yellower is the main active ingredient of Carthamus tinctorius L., which is proved to exhibit high value in many fields. However, it still appears some questions at the process of the development and utilization of safflower yellower products, such as low extraction efficiency, low purity of product, poor product stability and low bioavailability in vivo. In this paper, the extraction and purification technology of saffower yellower were studied; the saffower yellower niosomes were prepared; the pharmacokinetics and tissue distribution of saffower yellower niosomes were investigated after intravenous injection.In terms of extraction, different extraction methods were investigated and compared, the extraction process was optimized by central composite design. The optimum conditions were as followed:extraction temperature 61℃, extraction time 1.4h, solid-liquid ratio of 1:30, the extraction of safflower yellow was 14.60mg/g. In the aspect of purification, the macroporous resin method and clarifying agent precipitation method were studied and optimized by the orthogonal design and the central composite design respectively. The optimum technology of macroporous adsorption resin method: eluent flow rate of 1.5mL · min-1, the sample ratio of 1:30, the type of eluent 15% ethanol; the product recovery was 69.87%, with the purity of 47.54%. The optimum technology of clarifying agent precipitation method:clarifying agent 4%, stirring time 150min, clarifying agent 4%; the product recovery was 56.60%, with a purity of 57.32%. Eventually, the clarifying method was choosed to purify the safflower yellower.The safflower yellower niosomes were prepared by ethanol injection method. The encapsulation efficiency of niosomess as evaluation index was used to investigate the influence of experimental factors, and to optimize the technology by central composite design. The optimum technology:Tween80:cholesterol 5:1, bath temperature 55.5℃, drug concentration 1.55 mg·mL-1. The encapsulation efficiency of safflower yellower niosomes was 41.51±0.63%, average particle size was 115±4.7nm and the zeta potential was -29±2.1mV. Stability test showed that the niosomes were stored well at 4℃ for 1 month. The release test in vitro showed that the sustained-release effect in pH7.4 buffer solution was obvious.The pharmacokinetic study was carried out in rabbtis, the drug clearance rate CL of niosomes and solution was 1.08 mL·min-1 and 1.21 mL·min-1, the elimination phase half-life t1/2 was 45.20min and 66.97min, the area under concentration-time curve AUCo-t was 1796.97 ug·min/mL and 2355.24 ug·min/mL, respectively. It suggested that the nonionic surfactant niosomes slowed down the elimination rate of safflower yellower, and prolonged the circulation time of safflower yellower in vivo. The tissue distribution was investigated in mice, the results showed that, the drug concentration of noisomes group was higher in liver and spleen compared with the solution group (P<0.05), while less change in heart and kidney. It suggested that the niosomes exhibited certain targeting property and provide a research direction for the application of safflower yellow in the liver.