Antisolvent Nanoprecipitation Preparation And Oral Bioavailability Of Ursolic Acid Nanoparitlces

Ursolic Acid,is a pentacyclic triterpene compound,has anti-tumor,antiinflammatory,antibacterial,immune regulation and many kinds of biological activity.But it is insoluble in water,the oral bioavailability is only 0.7%,greatly influenced its application in clinical practice.In order to improve the oral bioavailability of ursolic acid,prepared nanoparticles via the antisolvent precipitation with TPGS1000 or P188 as a stabilizer.Take the average particle size,particle size distribution(PDI)and Zeta potential as evaluation index,optimize the the process of preparation and prescription,the suspension are stability and uniform(Zeta potential-20~-25 mV),size distribution(PDI<0.2),the average particle size are 127 nm(TPGS1000)and 140 nm(P188).The microscopic and physicochemical properties of ursolic acid nanoparticle were charactered by scanning electron microscope(SEM),X-ray diffraction(XRD),differential thermal scanners(DSC)and infrared spectrometer(FTIR).Proved that nanoparticles are uniform and the morphology is round,the process of preparation did not have effect on chemical structure of ursolic acid,however,it was changed from rhombic to partically amorphous.Nanosuspension belongs to the unstable thermodynamic system,in order to improve its stability and the shelf life using freeze drying method to make them into powder.Take the appearance,redispersibility and SEM images as evaluation index,study the effect of single or two kinds of freeze-drying protectants combined on powder.Adding 10% trehalose in TPGS1000-UA nanosuspension,10% trehalose or 3% PEG2000 as freeze-dried protectant in P188-UA nanosuspension added,resulting the powder in good appearance,loose,no collapse and dispersion easily.The former dispersed suspension particle size was 239.2±5.2 nm,PDI=0.243±0.013,Zata potential-23.8±2.6 mV,the dispersed suspension measurement parameters of P188-UA dispersed suspension respectively are 228.4±9.8 nm,PDI=0.399±0.022,Zata potential-23.8±3.1 mV and 208.1±8.6 nm,PDI=0.335±0.025,Zata potential-31.6±3 mV.In vitro release experiments proved that there is no significant difference(P>0.05)between redispersed and fresh naonosuspension during the release process,but P188-UA nanosuspension released slowly than TPGS1000-UA nanosuspension.In vivo rat experiment,the concentration of drug in blood-time curve area(AUC0-12)of TPGS1000-UA nanoparticle suspension compared with raw materials is about 26 times,the AUC0-12 of P188-UA nanoparticle suspension compared with the raw material is about 2 times.The results showed that TPGS1000 promoted the absorption of ursolic acid significantly and improve its bioavailability.