Prepartion And Preliminary Evaluate On Quality Of Uox-loaded Hollow Nanospheres

Uricase(UOX)is a key enzyme in purine metabolic pathways and can catalyze uric acid into allantoin.It is widely found in plants,fungi,bacteria and some mammalian tissues.While human body lacks UOX,the concentration of serum uric acid will significantly increased and cause hyperuricemia sparking a series of diseases when production of uric acid is increased or excretion of uric acid process is blocked.Because UOX has merit of strong specificity and high catalytic efficiency,it can be used for the treatment of hyperuricemia.However,UOX also has some defects just like poor stability,short active half-life in vivo,low bioavailability etc,deciding it need frequent dosing to maintain an effective blood concentration.The self-assembly hollow nanospheres is a novel drug carrier which could encapsulate enzymes,it shows the advantages of the similarity between biological membranes,improving the drug stability,reducing drug toxicity and immunogenicity.In order to overcome the shortcomings of UOX and expand its clinical application,the self-assembly HA-g-PEG/HPCD hollow nanospheres loaded with UOX firstly(UHPHDs)was studied preliminary.This paper mainly includes the following sections:In Chapter ?,the preparation and physicochemical properties of UHPHDs were studied.The results showed that UHPHDs was evenly distributed round or oval,and its particle diameter was(299.60±13.05)nm,the Zeta potential was(-45.10±2.75)mV and the entrapment efficiency was(62.17±2.94)%.In Chapter ?,the optimum temperature and optimum pH of UHPHDs were studied.The results showed that the optimum temperature of UHPHDs was 40?,the optimum pH of UHPHDs was 8.5.The activity of UHPHDs was higher than UOX at the same temperature and pH value.In chapter ?,the stabilities of UHPHDs in vitro were studied.The thermal stability,storage stability,pH stability,proteolytic stability and the effectt of several metal ions and organic compounds were investigated.The result showed that the activity of UHPHDs was significantly higher than that of the UOX under the same conditions.In Chapter ?,the enzyme kinetics and pharmacokinetic of UHPHDs were studied.The Km of UHPHDs and UOX were(12.97±2.31)?mol/L and(14.36±2.60)?mol/L,which showed that the affinity of UHPHDs was better than that of UOX.The result of pharmacokinetic showed that UHPHDs can improve the pharmacokinetic properties of the UOX and it also can improve the relative bioavailability compared with UOX remarkably.In Chapter ?,the pharmacodynamics in vivo was studied.The pharmacodynamic result showed that UHPHDs and UOX can reduce uric acid level in the model rats and UHPHDs was significantly superior in decreasing the serum uric acid level to UOX.