| Artemisinin is a sesquiterpene lactone containing peroxy group.In the early 1970s,artemisinin was extracted from Artemisia annua for the first time by famous pharmacists in China,and it was named artemisinin.It is also the best natural bioactive substance for the treatment of cerebral malaria and chloroquine falciparum malaria in the world.Recent studies have shown that artemisinin and its derivatives play an important role in the treatment of lupus erythematosus,antibacterial and tumor.However,due to its high fat solubility,poor solubility in water and low bioavailability,artemisinin can be quickly metabolized out of the body,which greatly affects the utilization and development of artemisinin.The main content of this paper is the preparation of porous starch loaded with artemisinin hydroxypropyl-β-Cyclodextrin inclusion complex(artemisinin HP)-β-Artemisinin through hydroxypropyl group-β-After cyclodextrin inclusion,the porous starch was loaded to improve the water solubility of artemisinin.Then,the characterization,tissue distribution,in vitro and in vivo antimalarial activity of the porous starch loaded artemisinin HP-β-CD inclusion complex were studied:1.The preparation process of AHPS was optimized as follows:the molar ratio of HP-β-CD to artemisinin was 2:1,ethanol was removed by mixed suspension evaporation method,the unincluded HP-β-CD was washed with a small amount of water and absolute ethanol,and artemisinin was dried at low temperature to obtain the white product artemisinin HP-β-BCD inclusion complex.After that,3.5 mg/ml of artemisinin HP-β-CD inclusion compound was put into the adsorption system containing 187.25 mg/ml porous starch.The reaction system was ultrasonicated in an ultrasonic machine at 37℃ for 30 min.a rotor was added into a 50 ml centrifuge tube,and the sealing film was sealed.The reaction system was placed in a constant temperature water bath magnetic stirrer for adsorption for 40 min at 37℃.AHPS was obtained after low temperature drying.Under the optimum conditions,the porous starch loading of AHPs was 23.58%.2.The physical and chemical properties of the AHPS were characterized by SEM,BETt,FTIR,XRD,DSC and TG.The results show that only physical changes occur in the process of loading HP-β-CD inclusion complex with porous starch,and the chemical structure of artemisinin is not changed.The results of XRD,DSC and TG were also verified again.Artemisinin was loaded by porous starch completely by HP-β-CD,so it showed that it had the same amorphous structure as porous starch,thus improving the water solubility of artemisinin.3.The results showed that the saturated solubility of AHPS in water,artificial gastric juice and artificial intestinal juice were 2.56,2.32 and 1.35 times as much as that of artemisinin powder,2.41,2.12 and 1.23 times as much as that of artemisinin piperaquine tablets,and 1.85,2.12 and 1.18 times as much as that of dihydroartemisinin.The dissolution rates of artemisinin in water,artificial gastric juice and artificial intestinal juice were 3.11,2.54 and 1.35 times of artemisinin powder,2.53,2.39 and 1.18 times of artemisinin piperaquine tablets,and 1.90,1.93 and 1.23 times of dihydro-artemisinin,respectively.4.In the study of the bioavailability of AHPS in rats,the concentrations of bioactive moLecules in heart,liver,spleen,lung,kidney,brain and six tissues of rats were detected at different time after oral administration of artemisinin,artemisinin piperaquine tablets and AHPS.The results showed that after intragastric administration at the same time,AHPS detected higher concentration of artemisinin than other drug groups,and the residence time in vivo was longer.The results showed that AHPS changed the particle size of artemisinin and increased its water solubility.Therefore,the bioavailability of artemisinin in various tissues and organs was greatly improved.In the study of bioavailability of HP-β-CD inclusion complex loaded with porous starch in rats,the rats were given artemisinin,dihydroartemisinin,porous starch loaded artemisinin,artemisinin piperaquine tablets and porous starch loaded with HP-β-CD inclusion complex,and then the hearts,liver,spleen,lungs,lungs and the heart,liver,spleen,lung of rats were detected at different time The biological activity moLecular concentration of kidney,brain and 6 tissues.The results showed that the content of artemisinin loaded with porous starch was detected in the tissues and organs of rats after gavage at the same time,which was higher than that of other drugs.The results showed that the porous starch loaded with artemisinin HP-β-CD inclusion complex changed the size of artemisinin particle size and increased the concentration of artemisinin Its water solubility,therefore,the bioavailability of the organism in various tissues and organs has been greatly improved.5.In the study of antimalarial activity of AHPS,two methods in vitro and in vivo were used.The results of antimalarial activity in vitro showed that the antimalarial activity of AHPS against Plasmodium falciparum 3D7 was slightly better than that of dihydroartemisinin,and far better than that of artemisinin.The results showed that compared with artemisinin group and dihydroartemisinin group,AHPS could significantly prolong the survival time,reduce the Plasmodium level,and improve the RMCBS score Blood smear showed that it could kill Plasmodium and improve the body weight of mice.The survival rate of AHPS group was even 100% on the 14th day,and the body weight was the lowest on the 14th day after inoculation.The rmcbs score of AHPS group was also significantly better than that of artemisinin group and dihydroartemisinin group,indicating that AHPS can improve the clinical symptoms and signs of ECM mice. |
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