Study On Breviscapine-loaded DSPE-PEG Polymeric Micelles

Objective:Breviscapine(Bre)is a flavonoid component isolated from Asteraceae breviscapus,used for clinical treatment of cerebral embolism,sequelae of stroke,coronary heart disease and other ischemic and microcirculatory disorders Better efficacy and safety.Breviscapine preparations currently on the market include oral preparations and injections,which have problems of low bioavailability and short half-life.As a new drug delivery system,polymer micelles have the advantages of hydrophilic shell,small CMC value,and nanometer particle size of 10-100 nm.The hydrophilic shell prevents the aggregation of polymer micelles in the solution,reduces the adsorption of proteins on the surface of the polymer micelles and the attachment of cells,thereby prolonging the circulation time of the drug in the body and maintaining stability.DSPE-PEG 2000 is a medicinal polymer material approved by the US FDA.It is non-toxic,non-immunogenic and non-antigenic.It is commonly used to wrap proteins,peptides and other drugs.In view of the characteristics of breviscapine’s poor water solubility and fat solubility and short half-life,DSPE-PEG was used as a carrier material to encapsulate breviscapine,to prepare breviscapine DSPE-PEG polymer micelles,and to investigate its drug release properties and pharmacokinetics Academic nature.Methods:1.Establish the analytical method of Breviscapine(bre)by HPLC.2.Prepare breviscapine(bre)polymer micelles by film hydration,and determine theencapsulation efficiency and drug loading of breviscapine(bre)polymer micelles.Orthogonal design was used to screen out the optimal preparation process of Breviscapine(bre)polymer micelles.3.Using dialysis to investigate the in vitro drug release behavior of Breviscapine(bre)polymer micelles.4.Establish breviscapine(bre)detection method in rat plasma by HPLC method and calculate pharmacokinetic parameters.Result:1.The precision of Breviscapine(bre)RSD <3%,the method recovery rate RSD <3%.2.The encapsulation efficiency of the prepared Breviscapine(bre)polymer micelles is(83.78 ± 2.52)%,and the drug loading is(14.30 ± 1.89)%(n = 3).The best preparation process of Breviscapine(bre)polymer micelles is 1: 5 drug-to-carrier drug ratio,the buffer solution is distilled water,the buffer volume is 8 ml,and the water bath temperature is 37 ℃.The encapsulation efficiency of Breviscapine(bre)polymer micelles prepared under this condition can reach 84.61%.3.In vitro release results: The cumulative release rates of the API and Breviscapine(bre)polymer micelles at 5h were 86.76% and 57.89%,respectively;the cumulative release rates of the API and Breviscapine(bre)polymer micelles at 24 h were 100.0%and 75.35%.4.Pharmacokinetic results: Breviscapine(bre)API(t 1/2)is 0.357 ± 0.05,AUC0-∞ is1712.676 ± 137.342,MRT0-∞ is 0.454 ± 0.028;Breviscapine(bre)injection Liquid(t1/2)is 1.017 ± 0.088,AUC0-∞ is 4668.887 ± 230.638,MRT0-∞ is 1.211 ± 0.063;Breviscapine(bre)polymer micelle(t 1/2)is 4.125 ± 0.152,AUC0-∞ is 10875.705 ±165.34,MRT0-∞ is 5.488 ± 0.093.Breviscapine(bre)polymer micelle elimination half-life(t 1/2)was extended from 0.357 h to 4.125h(p <0.05).The AUC0-∞ of Breviscapine(bre)polymer micelle is 10875.705 ug h / L,which is 6.3 times higher than that of free Breviscapine(bre)and 2.32 times higher than Breviscapine(bre)injection.In addition,the breviscapine(bre)polymer micelle MRT is 12.1 times(p<0.01)the breviscapine(bre)API.Conclusion:The breviscapine(bre)analysis method established by UV method and HPLC method is reliable.The breviscapine(bre)polymer micelles prepared by film hydration method have good repeatability.The polymer micelles prepared according to the optimal preparation process have good encapsulation efficiency.Breviscapine(bre)polymer micelles prepared by thin-film hydration have good drug-loading properties.The results of in vitro drug release behavior studies show that,compared with breviscapine(bre)APIs,breviscapine(bre)polymers Micelles can delay drug release.The results of pharmacokinetic studies showed that compared with breviscapine(bre)drug substance,breviscapine(bre)injection,breviscapine(bre)drug substance polymer micelles eliminated the prolonged half-life in rats.