Preparation And In Vitro/in Vivo Evaluation Of Quercetin Nanoemulsion

Quercetin（QT）is a kind of polyhydroxy flavonoid widely distributed in plants,which has a variety pharmacological effects,such as antioxidant,anticancer,anti-inflammatory,and plays a obvious role in improving cognition.QT has the characteristics of low solubility and high permeability,and its poor water solubility leads to slow rate of dissolution and a poor bioavailability,which limits its development and application.The fabrication process of nanoemulsions（NE）is simple,which can not only improve the solubility of insoluble drugs,but also can increase the absorption and transport of drugs in the body.Therefore,NE has been widely applied in many fields,such as food,pharmaceutical.In this paper,QT-NE was prepared from QT.This approach can improved its insoluble characteristics,increased its solubility and bioavailability,and to investigate the effect on scopolamine-induced mild cognitive impairment in mice.HPLC was used to determine the QT content in vitro,the blank NE composed of ethyl oleate,Tw-80 and PEG400 was determined through a solubility test,compatibility study and pseudo-terpolymer phase diagram.The mass percentage of the oil phase and the value range of Km were determined by a pseudo-ternary phase diagram.On this basis,the central composite design was used to further optimize the prescription with particle size and PDI as indicators,and the optimal prescription of QT-NE was ethyl oleate:Tw-80:PEG400:water whose ratio was 7.3%:23.2%:6.8%:62.7%.The quality evaluation of the QT-NE prepared by the optimal formulation,the result showed that the appearance of QT-NE is pale yellow clear,an O/W emulsion of QT-NE is formed.QT-NE showing a nearly spherical shape under the transmission electron microscope.The particle size and polydispersity indexes were（13.06±0.50）nm and0.207±0.008 respectively.The results of in vitro dissolution showed that the amount of cumulative dissolution of QT from QT-NE was significantly enhanced（P<0.01）,compared with that of raw QT,indicating that QT-NE can improve the release of QT-NE in vitro.The pharmacokinetics of QT-NE in rats was been studied preliminarily.The results showed that after oral administration,the AUC_{（0-24 h）}of QT-NE group was significantly increased（P<0.01）,which was 4.16 times higher than that of raw QT,and the C_max of QT-NE group was also significantly increased（P<0.01）,which was 3.69 times higher than that of raw QT.The single-pass perfusion model was established in rats to investigate the intestinal absorption characteristics of QT-NE.Our results suggested that the best absorption of QT-NE was in the ileum segment,followed by the colon segment and the duodenum segment,and the worst absorption was in the jejunum segment.Compared with raw QT,the K_a and P_app of QT-NE had a significant improvement（P<0.01）,indicating the NE can improve the absorption of QT in the intestinal tract.We investigated whether QT-NE can improve the learning and memory ability of mice with cognitive impairment induced by intraperitoneal injection of scopolamine.Morris water maze test was used to conduct the behavioral investigation.The contents of relative enzymes in brain tissue of mice were determined by ELISA,and the pathomorphological changes in the hippocampal CA1 region were observed by Nissl-staining.The results showed that compared with the model group,QT-NE could significantly shorten the escape latency of mice,extend the quadrant dwell time and increase the number of platform crossings（P<0.01）,increase the level of SOD,GSH-P_X,CAT,and ACh in the brain tissue of mice,and decrease the activity of MDA and ACh E,and the damage of neurons cells in the hippocampal CA1 region was significantly improved.In summary,the preparation technology of QT-NE is stable and the quality is controllable,which can significantly improve the solubility and dissolution of QT,and improve the bioavailability and intestinal absorption of QT in rats,and it is give full play to the cognitive effect of QT in mice.