| Mangiferin is found in a variety of natural drugs,such as Anemarrhena,Phellodendron,Radix Polygoni,etc.In recent years,researchers have found pharmacological effects of mangiferin in anti-inflammatory,anti-oxidative,anti-tumor,anti-diabetes,anti-AIDS,and so on.However,mangiferin is extremely poor in water solubility and insoluble in non-polar solvents,leading to very low oral bioavailability.In order to increase the solubility of mangiferin and improve its oral bioavailability,mangiferin was prepared into nanoparticles and its dissolution in vitro and pharmacokinetics and tissue distribution in vivo were investigated.The main contents and results are as follows:1.A high performance liquid chromatography method was established for the determination of mangiferin in vitro.The method has high accuracy,good repeatability and good precision.It can be used for the determination of mangiferin in vitro.The equilibrium solubility and oil-water partition coefficient of mangiferin were studied before the prescription,and the entrapment efficiency and drug loading capacity of mangiferin nanoparticles were determined.The results showed that the oil-water partition coefficient of mangiferin varied with p H value.But the whole level is very low,which may be one of the reasons for its low bioavailability.2.In order to improve the solubility and bioavailability of mangiferin,the preparation of mangiferin was prepared by the method of compound emulsion and solvent volatilization.The preparation process and the range of prescription factors were screened by single factor test,and the formulation was further optimized by Box-Behnken response surface method.The optimum preparation prescription of mangiferin nanoparticles was obtained as follows: the size of mangiferin nanoparticles prepared by this prescription was uniform,the whole system was stable,and the deviation between the entrapment efficiency,the actual value of drug loading and the predicted value was within ± 5%.The solubility and oil-water partition coefficient of mangiferin nanoparticles were 1.79 and 2.04 times higher than those of mangiferin,respectively.The dissolution test in vitro showed that the cumulative dissolution rate of mangiferin nanoparticles was 1.48 times higher than that of mangiferin.3.The content of mangiferin in rat plasma and tissues was determined by HPLC method.The results showed that no endogenous substances were detected in plasma and tissues for mangiferin.In this method,extraction recoveries were more than 75%,the recovery rate was between 85%-105%.The detection of biological samples can be used for the determination of mangiferin in rats with good repeatability,stability and precision.4.The results of pharmacokinetic study showed that after intragastric administration of mangiferin nanoparticles and raw materials in rats,There was a significant difference between two groups(P<0.01).The AUC(0-t)and AUC(0-?)of mangiferin nanoparticles were 1.63 and 1.62 times as much as those of API,respectively.The apparent distribution volume(Vz/F)and clearance rate(CLz/F)of mangiferin nanoparticles were decreased by 1.72 and 1.61 times,respectively.The results showed that the distribution range of mangiferin nanoparticles in vivo was narrower than that of raw materials,and the retention time of mangiferin nanoparticles in vivo was longer than that of raw drugs.The bioavailability of mangiferin nanoparticles was greatly improved.The relative bioavailability of mangiferin nanoparticles was 162.46%.The distribution time in all tissues was almost kept at about 1 h for mangiferin nanoparticles and raw materials after intragastric administration.Mangiferin nanoparticles increased the distribution of mangiferin in liver,brain and pancreas,but decreased in lung and spleen. |
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