Preparation And Performance Study Of Azoxystrobin Microspheres With Slow-release Function By Electrostatic Spray Technology

As a methoxy acrylate fungicide,azoxystrobin is widely used because it has good activity against almost all fungal diseases.However,due to the low water solubility of traditional pesticides and other factors such as spray drift,runoff,photolysis and microbial degradation,a large number of pesticides failed to reach the target location,which not only caused huge economic losses and waste,but the lost pesticides would also cause serious environmental issue.In this study,the innovative use of high-voltage electrostatic spray technology to prepare drugloaded microspheres.The microspheres can significantly increase the duration and utilization of the drug because of its sustained release performance.In this study,three materials:polyacrylonitrile,sodium alginate and polycaprolactone were selected as polymer carriers,prepared azoxystrobin-loaded polyacrylonitrile microspheres,azoxystrobin/sodium alginate coreshell microspheres and azoxystrobin/polycaprolactone core-shell microspheres by electrostatic spray technology.The release rules of azoxystrobin in buffer solutions of p H=5(P1),p H=7(P2)and p H=8(P3)were studied respectively.After comparison,polycaprolactone microspheres,the best carrier for drug release,were selected for in vitro drug activity study.The research results show that the use of high-voltage electrostatic spray technology to prepare drug-loaded microspheres has practical significance and feasibility,and provides a technical path for pesticide reduction and efficiency.The main research contents are as follows:1.Preparation and research of azoxystrobin/polyacrylonitrile microspheres.Using polyacrylonitrile as the carrier,the polyacrylonitrile-loaded azoxystrobin microspheres with a diameter of 860 nm were prepared by uniaxial electrostatic spray technology.The drug-loaded microspheres have good roundness,smooth surface and good drug loading.The best experimental conditions are: the concentration of polyacrylonitrile solution is 2 w/v%,the mass ratio of azoxystrobin to polyacrylonitrile is 2:1,the injection rate is 1.25 ml/h,the working distance is 20 cm and the working voltage is 15 k V.The working voltage and the mass ratio of azoxystrobin and polyacrylonitrile have an effect on the particle size and drug loading of the drug-loaded microspheres.When the working voltage is 13 k V and 15 k V,the particle size of the microspheres are 1.32±0.075 μm and 0.86±0.084 μm respectively;when the mass ratio of azoxystrobin to polyacrylonitrile was 1:2 and 2:1,the drug loading was 26.59±0.36% and 34.53±1.31%,respectively.At 60 min,the cumulative release rate of polyacrylonitrile drug-loaded microspheres in P1,P2 and P3 release media reached 18%,50% and 58% respectively;however,the azoxystrobin only released 80%,75% and 70%,respectively.2.Preparation and research of azoxystrobin/sodium alginate core-shell microspheres.Sodium alginate is selected as the carrier,and azoxystrobin/sodium alginate microspheres are prepared by coaxial electrostatic spray technology.The preparation conditions are as follows: the shell layer sodium alginate concentration is 2 w/v%,the core layer is 2 w/v% azoxystrobin/sodium alginate mixed solution,the shell-core solution rate ratio is 1:1.5,and the voltage is 18 k V.The drug-loaded microspheres maintain good roundness in morphology,and the surface of the microspheres is not flat.The particle diameter of the drug-loaded microspheres is 44.4 μm.The working voltage and the core-shell solution advance rate ratio have an effect on the diameter of the microspheres and the drug loading.The diameter of the drug-loaded microspheres decreases with the increase of the working voltage,and the drug-loaded amount decreases with the decrease of the core-shell flow rate ratio.The cumulative release rate and release behavior of drug-loaded microspheres under different p H release solutions indicate that the release rate of drug-loaded microspheres in acidic media is significantly better than that of alkaline and neutral media.After1500 min under acidic solution conditions,the cumulative release rate of azoxystrobin reached only 45%,while under neutral and alkaline conditions,the corresponding release rate reached approximately 28% and 12%.The release behavior is more in line with the Korsmeyer-Peppas kinetic model,and the drug release mode is dominated by diffusion,erosion,penetration and swelling.3.Preparation and study of azoxystrobin/polycaprolactone core-shell microspheres.Select polycaprolactone as the carrier,and successfully prepared azoxystrobin-loaded polycaprolactone microspheres by coaxial electrostatic spray technology.Fluorescence microscopy analysis showed that the prepared drug-loaded microspheres had a core-shell structure,and azoxystrobin was effectively encapsulated in the carrier.Fourier transform infrared spectroscopy confirmed the combination of azoxystrobin and polycaprolactone,and thermogravimetric analysis showed that the presence of azoxystrobin would not affect the stability of polycaprolactone microspheres.The concentration of polycaprolactone,working voltage and receiving distance all affect the diameter of drug-loaded polycaprolactone.The best preparation conditions are as follows: the shell solution is 14 wt% pure polycaprolactone solution,the core solution is 4 wt% azoxystrobin solution,the working voltage is 10.6 k V and the receiving distance is 300 mm.The drug-loaded microspheres maintain good roundness and good dispersibility in the morphology,the surface is smooth without obvious cavities and wrinkles,the particle size of the drug-loaded microspheres is about 2.45 μm.The diameter of the drug-loaded microspheres decreases as the working voltage increases.The cumulative release of drug-loaded microspheres in different p H release solutions: at 60 min,compared with the cumulative release rate of azoxystrobin,the cumulative release rate of azoxystrobin in the drug-loaded microspheres only reached 8%(P1),12%(P2)and 18%(P3),while the cumulative release rate of azoxystrobin has reached 60%.After 2500 min,the cumulative release rate of polycaprolactone drug-loaded microspheres only reached 45%.The microspheres loaded with azoxystrobin showed slow and sustained release.The release behavior is more in line with the Korsmeyer-Peppas kinetic model,and the release mode indicates that the release is caused by non-Fickian diffusion.4.Polycaprolactone-loaded azoxystrobin microspheres were tested against Botrytis cinerea in vitro,and the results showed that compared with the blank group,the polycaprolactone microspheres loaded with azoxystrobin continued to inhibit the growth of the plant pathogenic bacteria B.cinerea mycelium for more than 7 days.It was further verified that the polycaprolactone carrier can realize the slow release of azoxystrobin and improve the utilization rate of pesticides.