The Study Of Syringopicroside Loaded Plga Nanoparticle For Pharmacokinetic,liver Targeting And Pharmacodynamics

Syringopicroside(SYR)is the component extracted and separated from clove leaf,which is a kind of herb.SYR have liver protective,cholagogic,anti-inflammatory,anti-viral and other effects,without side effects.However,due to the heavy oral dose administration of syringopicroside and the fact that biological half-life becomes short and bioavailability is low after intravenous injection,its therapeutic effect is weakened and its widespread application in clinical practice is limited.Previous study of our research group prepared SYR-PLGA-NP with encapsulation efficiency measuring at 61.1±1.21%,drug loading 6.01±0.21%.It typically presents the form of solid spherical particles under observation of a transmission electron microscope,with a relatively uniform distribution,and its average diameter is 133.4±0.97 nm.This research,based on the forming process PLGA nanoparticles,intends to make a study on the pharmacokinetics,liver targeting and pharmacodynamic of SYR-PLGA-NP.1 Pharmacokinetic studies on SYR-PLGA-NPWith SYR saline solution as a control group,this research studies the pharmacokinetic parameters of SYR-PLGA-NP,by drawing blood from the orbit of rat at the designed time point,by adopting HPLC to measure the concentration of SYR drug in whole blood and by utilizing 3P97 pharmacokinetic software to process the drug pharmacokinetic parameters and as well as to fit pharmacokinetic parameters.The results show that the drug process of SYR-PLGA-NP conforms to the dynamic characteristics of two-compartment model.With the same dose administration,the elimination half-life of T1/2? in rats of the SYR-PLGA-NP group is significantly prolonged compared with the SYR group.The significant increase of AUC indicates that the lifetime of the drug in organism has been extended after the drug is made into nanoparticles by extending the residue time in organism,thus improving the utilization efficiency.SYR-PLGA-NP can change the pharmacokinetic profile of the drug in rat,prolong the half life of the drug,increase the bio availability of the drug to extend the residence time of the drug in the circulatory system in the body,and reduce the clearance rate,so that SYR can maintain a high blood concentration in the body for a relatively long time,thus having some sustained release effect2 Study on the distribution of SYR-PLGA-NP in vivoSYR-PLGA-NP and SYR solution are injected intravenously into mouse tail,the concentration of SYR in each organization is tested through HPLC and the accumulation of SYR in each organization in mice is calculated through trapezoidal method.The distribution of SYR in mice after SYR-PLGA-NP administration is evaluated through drug targeting index(re)and drug selectivity index(te).The results show that the te index of liver in both SYR group and SYR-PLGA-NP group are higher than 1.This on one hand indicates that SYR is more selectively distributed in the liver,which is consistent with the liver protective function of SYR,and on the other hand also sugests that SYR-PLGA-NP have increased the distribution of SYR in liver tissue,which better serves the function of liver targeting.3 Study on the targeting of SYR-PLGA-NPA fluorescent marker called FITC is added to SYR-PLGA-NP in the the preparation process to mark PLGA nanoparticles.FITC-labeled PLGA nanoparticles are injected intravenously through tail and OptiScan FIVE 1 fluorescence endoscopic confocal laser microscopy is utilized to observe the distribution of gentiopicroside PLGA labeled by FITC in the major organs and cells in mice.Experimental results show that,FITC-labeled SYR-PLGA-NP accumulates mainly in the part of the liver while rarely in other parts,which suggests that FITC-labeled SYR-PLGA-NP is with relatively better liver targeting.And it can be observed at different time points that FITC-labeled SYR-PLGA-NP enters into the cell from outside,indicating that SYR is a kind of drug has a good liver targeting.4 Pharmacodynamic study on SYR-PLGA-NPIn the study on the pharmacodynamics of SYR-PLGA-NP,ELISA is utilized to test the effect of SYR-PLGA-NP on CCl4 acute liver injury model.The aminotransferase levels of the SYR group,the SYR-PLGA-NP group and the negative control group are significantly different from that of CCl4 injury model group(p<0.01).And SYR-PLGA-NP group shows a significantly stronger reducing effect on the two enzymes-AST and ALT than the raw drug group(p<0.01).Histopathological examination shows that the hepatic cord in CCl4 liver injury group is in disorder,large numbers of liver cells around the central vein swell,liver cells have edema and inflammatory cell infiltration,and there is an obvious transformation into fat cells.The swelling liver cells and fat liver cells have been observed a significant reduction in drug administration group.The shape of cell is generally normal,with a slight inflammatory cell infiltration.The SYR-PLGA-NP group shows the best effect of liver protection.Through the pharmacodynamic experiment,this study indicates that SYR has strong anti-liver injury effects.This research not only provides scientific proof for the liver targeting study on innovative Chinese medicine for anti-liver injury drugs,but also provides references for liver targeting study on nano-soluble drug formulations.