Preparation And Function Of Delivery System Of Buckwheat Flavonoids Nanoemulsion

Nano drug delivery system can improve the therapeutic effect of drugs and overcome the problems,such as limited solubility,poor aggregation,poor stability,low bioavailability,poor biological distribution,and lack of selectivity.The purpose of this study was to design a reasonable and effective buckwheat flavonoids nanoemulsion delivery system,in order to increase solubility and bioactivity,improve drug release characteristics in vitro and in vivo,and improve oral bioavailability.The main contents of nanoemulsion preparation and functional research are as follows:1.Firstly,the buckwheat flavonoids nanoemulsion were prepared and optimized.The constituents of the nanoemulsion were preliminarily screened by the saturated solubility method,and the pseudo-ternary phase diagram was used to further confirm the constituents and composition ratios.Castor oil was selected as the oil phase,PEG 40 hydrogenated castor oil was used as the surfactant,and 1,2-propanediol was used as the cosurfactant.The K_mof surfactant/cosurfactant was 3:1.The preparation process was optimized using the central composite design,with the particle size and encapsulation efficiency as evaluation indicators.Design-Expert software was used to fit the multiple regression equation model,and the the preparation and optimization of nanoemulsion was obtained through analysis of variance,significance test,effect surface analysis and optimization verification.2.The characteristics of buckwheat flavonoids nanoemulsion were evaluated.It was evaluated in terms of particle properties,physical and chemical properties and stability.The particle properties evaluation shows that the appearance of nanoemulsion is pale yellow and bright liquid,and the droplet shape was nearly spherical,with uniform particle size distribution and good dispersion observed by transmission electron microscope.The diameter of the nanoemulsion was 22.90 nm,the polydispersity index(PDI)was 0.22,and the Zeta potential was–22.08 m V.Physical and chemical properties of the nanoemulsion showed good performance,which the turbidity,p H,surface tension,electrical conductivity and other measured values were within the required range,and the encapsulation efficiency reached 98.11%.The stability evaluation showed that there was no stratification,turbidity and precipitation in nanoemulsion under different temperatures,speeds and dilution multiple.The results showed that the nanoemulsion particles were uniformly dispersed with particle sizes ranging from 10 to 100nm,nearly spherical or spherical,with the prescribed physicochemical properties,high encapsulation rate and good stability,which could be further used in the functional analysis of nanoemulsion preparation.3.In the antioxidant and antibacterial activity of buckwheat flavonoids nanoemulsion,we set nanoemulsion sample group and suspension control group to evaluate its function.The study showed the nanoemulsion has certain antioxidant activity,with the test of DPPH scavenging activity,hydroxyl radical scavenging activity,and superoxide anion scavenging activity.The antioxidant activity of nanoemulsion was obviously better than the suspension control group,and DPPH scavenging activity and hydroxyl radical scavenging activity were higher than the superoxide anion scavenging activity.The antibacterial activity of buckwheat flavonoids nanoemulsion were test through the determination of MIC and MBC,the agar disc diffusion Test,and the time killing Assay.A gram-positive bacterium(Staphylococcus aureus ATCC 6538),a gram-negative bacterium(Escherichia coli 8099),and a fungus(Candida albicans ATCC 10231)were were used to detect antibacterial activity.The results showed that buckwheat flavonoids nanoemulsion was superior to the control suspension of the corresponding concentration in the bacteriostatic diameter,MIC and MBC value and antibacterial activity of the three bacteria,and the nanoemulsion could not only inhibit the growth of the three bacteria,at the same time,it also has a certain long-term antibacterial activity.4.The release performance of buckwheat flavonoids nanoemulsion in vitro was studied by dynamic dialysis method,and the drug delivery model was simulated in order to fit the release of drug in gastrointestinal tract after oral administration,with the indexes of correlation coefficient R²,residual sum of squares(RSS)and Akaike information criterion(AIC).In the cumulative release curve in vitro,the cumulative release of the nanoemulsion increased gradually with time,reaching 88.16%at 48 h,while the cumulative release of the suspension was only 15.14%under the same conditions.The results showed that the cumulative release of nanoemulsion was 5 times that of suspension,and the drug release effect was significantly better than suspension,and the release showed a long-term trend of slow release.The fitting results of dynamic equation show that that drug release in nanoemulsion may follow Weibull model and is a continuous and dynamic release process.It is also possible to release according to the model of Ritger-Peppas equation and follow Fickian diffusion rule during release.5.In the study of pharmacokinetics and bioavailability in vivo,Wistar rats were randomly divided into groups and administrated.Blood was collected from fundus venous plexus within 48h at different time points,and plasma samples were processed and determined by high performance liquid chromatography.The pharmacokinetic parameters showed that the area under the curve(AUC)of the nanoemulsion and suspension were 1621.26±141.60ng/m L and 734.48±109.81 ng/m L.The maximum concentration of nanoemulsion and suspension were 156.15±8.14 ng/m L and 59.89±6.49ng/m L,respectively.The C_maxof nanoemulsion was 2.6 times that of the latter.The results showed that the effective absorption of buckwheat flavonoids nanoemulsion was 2.2 times higher than that of buckwheat flavonoids suspension without preparation,and the peak of blood drug concentration was 2.6 times higher than that of suspension,and the bioavailability of buckwheat flavonoids nanoemulsion in vivo was significantly improved.To sum up,buckwheat flavonoids nanoemulsion delivery carrier was constructed and optimized,and its characteristics were evaluated.The study of antioxidant and antibacterial activity showed that the nanoemulsion has higher antibacterial activity and free radical scavenging ability than that of the suspension.It was found that buckwheat flavonoids nanoemulsion had good particle size characteristics and physicochemical properties,good stability and high encapsulation rate,and the biological activity and bioavailability of buckwheat flavonoids nanoemulsion were significantly better than those of unprepared drugs.These results show that the nanoemulsion prepared in this paper can be used as an drug carrier in practice.