Preparation,Evaluation And Bioavailability Of Betulinic Acid Nanoparticles By Anti-Solvent Recrystallization

Betulinic acid also known as lupine is a kind of pentacyclic triterpenoid which extracted from the bark of platyphylla,ha-ving antioxidant,anti-tumor and anti-inflamnatory.The research shows that betulinic acid can inhibit tumor cell growth and induce angiogenesis against apoptosis,which shows the potential of betulinic acid in the field of cancer.But the poor solubility of betulinic acid limiting its bioavailability.This paper studies the preparation of betulinic acid nanoparticles by antisolvent precipitation process using ethanol as solvent and water as antisolvent,and optimizes the factors which infiuence the MPS of betulinic acid nanoparticles by a Single factor design.And the betulin nanoparticles powder obtained were characterized in vitro/in vivo,specific content as follows.1.Through a Single factor design optimize,The optimum conditions are determined as follows:concentration of genipin solution 3 mg/mL,volume ratio 3 times,stirring intensity 900 rpm,dropping speed of anti-anti-solvent 8 mL/min and reaction temperature 25 C.And the betulinic acid nanoparticles powder obtained were characterized using scanning electron microscopy(SEM),X-ray diffraction(XRD),Fourier transform infrared spectroscopy(FT-IR),Mass spectrometry(LC-MS),differential calorimetry(DSC)and thermogravimetric analysis(TG),dissolution test and solvent residual.The results show that the MPS of betulinic acid nanoparticles nearly spherical,average particle diameter of 363nm.2.In this paper,we compared the DPPH of betulinic acid nanoparticles to raw betulinic acid.The result showed that IC50 of raw betulinic acid was 782μg/mL,but IC50 of betulinic acid nanoparticles was 552μg/mL,so the DPPH of betulinic acid nanoparticles was better than raw betulinic acid,which demonstrates that nano improved the water solubility of betulinic acid,and increased its antioxidant activity.3.Dissolution study of raw betulinic acid and betulinic acid nanoparticles was determined by HPLC.Artificial gastric juice was used as dissolvent in this part.The result demonstrates that the betulinic acid nanoparticles showed a more rapid dissolution rates and higher solubility than the raw betulinic acid.Betulinic acid nanoparticles dissolution rate reached 93.97%,while raw betulinic acid dissolution rate was only 19.84%.4.In this paper,we also compared the bioavailability of betulinic acid nanoparticles to raw betulinic acid.In this part,the concentration of the betulinic acid in plasma of rat was detected by HPLC.And the results demonstrate that oral administration of betulinic acid nanoparticules leads to 196%increase in bioavailability.These results indicate that betulinic acid nanoparticles having a uniform particle size distribution,the water solubility,antioxidant and bioavailability of betulinic acid was improved significantly.