Study On Preparation And Pharmacokinetics Of Osthole Liposome

Liposome was a new microparticle drug delivery system similar to noisome, cholesterol and lecithin as the basic membrane material,assembled into a bilayer structure similar to the biological membrane structure in aqueous medium.Liposome could entrapment fat-soluble or warer-suluble drugs, delay the drug release in vivo, increase local blood concentration. After encapsulated by liposome,distribution of drugs could be changed.It was mainly swallowed by reticuloendothelial system. The targeting of drugs to liver, spleen, lung incresed and toxicity attenuated.This paper prepared the osthole liposomes: To investigate the effect of preparation method, prescription composition and preparation process of osthol liposome on encapsulation and research the permeability, release behavior in vitro, hemolytic test and pharmacokinetics of mice.1. Preparation and quality evaluation of osthole liposomeLiposomes were prepared by film ultrasonic dispersion method,encapsulation efficiency as the evaluation index. To choose prescription by orthogonal test and the optimized prescription was:the ratio of cholesterol and lecithin was 1:2, drug lipid ratio 3:20, p H 8.2, Film forming temperature 40℃. The optimized process was:hydration time 2 h,hydration temperature 40 ℃, ultrasonic time 5min, ultrasonic power 350 w. Encapsulation efficiency of osthole liposome was determined by low-speed centrifugation.The morphology of liposomes was observed by transmission electron microscopy, particle size and potential of liposome determined by Malvin particle analyzer. The results showed that the morphology of liposomes was complete spherical or ellipsoidal, the average particle size was 260.3±6.8 nm, mean potential-28.1±1.7 m V.The results of hemolytic test of osthole liposome in vitro showed that this preparation had a good hemolysis safety. Osthole liposomes were kept for 14 days at 4 ℃ and room temperature. The former had no delamination and precipitation phenomenon.Permeability were 1.5% 、 7.1%. The results indicated that osthole liposome kept well and had good storage at 4 ℃.Diffusion method of dialysis bag was used to investigate the osthol liposome release in vitro: 0.9% normal saline as release medium; release temperature 37±0.5 ℃; rotation rate 75 r·min^-1. The results indicated that osthole liposome has a certain sustained-release effect in vitro.Pharmacodynamic test of osthole liposomes:Lipid peroxidation was the product of polyunsaturated fatty acids of membrane damaged by free radicals. Determination of lipid peroxidation in biological tissue, MDA, was an important indicator of the evaluation of aging drug, and an important sign of detecting aging biological tissue. The literature showed that osthole can significantly reduce the lipid peroxidation of brain and liver in mice. According to the literature,adding free osthole and osthole liposome respectively to brain and liver of mice in vitro to finish pharmacodynamic test. Observing the reducing effect on the lipid peroxidation and camparing the results. The experimental data was measured by SPSS statistical analysis software, and the results showed that the experimental group and the control group were significantly different（P<0.05）, which indicated that both drugs had obvious inhibition effect on the lipid peroxidation. Osthole liposome had better pharmacodynamic effects than osthole. At present, except for oral preparations, osthole had no other safe preparation. This experiment filled the blank of osthole liposome preparation, at the same time, provided basic data for preparing large-scale osthole liposomes in the future, layed the foundation for safely and effectively use of osthole in clininal.2. Pharmacokinetic studies of osthole liposomes in mice in vivoUsing self-made osthole solution as the control preparation to study the pharmacokinetics in mice. The results was dealed by 3p97 pharmacokinetic software. The fitting results of compartment model showed that both osthole and osthole liposome fit two compartment model with a weight coefficient of 1. The elimination half-life of osthole liposome and osthole were 31.39 min and 18.22 min, Clearance rate were 0.048 m L·min^-1and 0.06 m L·min^-1. This indicated that osthole encapsulated by liposome can slow the process of drug elimination in vivo. Results of statiscal analysis showed that AUC of osthole liposome and osthole were 148.08 μg·min·m L^-1 and 112.25 μg·min·m L^-1, MRT were 31.01 min and 18.53 min. Pharmacokinetic parameters of osthole and osthole liposome had statistically significant difference.