Study On The Preparation And Properties Of Nanosheres Loaded With Insoluble Pesticides

Pesticides are widely used in agriculture to ensure the yield and quality of crops.However,pesticide prodrugs generally have the disadvantages of poor water solubility and stability,and most of them cannot be applied directly and need to be processed into various dosage forms.However,traditional dosage forms often incorporate toxic organic solvents and additives,which have substantial negative impacts on ecosystems,low acti-ve ingredient utilization and lead to irreversible toxicity to non-target species.Therefore,the development of a drug delivery system that can effectively solve many problems of pesticides is an urgent need for sustainable agricultural development.In this study,the commonly used pesticide insecticide fipronil(FP)was used as a model drug,cyclodextr-in/chitosan nanomicrospheres loaded with FP were prepared,and the main research contents and results are as follows:(1)β-cyclodextrin(β-CD)and hydroxypropyl-β-cyclodextrin(HP-β-CD)were sel-ected to react with monochloroacetic acid to prepare anionic derivatives:carboxymeth-yl-β-cyclodextrin(CM-β-CD)and carboxymet-hylhydroxypropyl-β-cyclodextrin(CM-HP-β-CD),respectively.The substitution degree was used as an evaluation index to optimize the preparation process.CM-β-CD and CM-HP-β-CD with substituteon degre-es of 5.68 and 2.73,respectively,were obtained and structureally verified by infrared sp-ectroscopy(FT-IR)and nuclear magnetic resonance hydrogen spectroscopy(~1H NMR).(2)The FP with CM-β-CD and CM-HP-β-CD were prepared as inclusion complex-es(ICs):CM-β-CD/FP ICs and CM-HP-β-CD/FP ICs.The A_L-type curves were obtained by phase solubility studies,indicating that FP andβ-CD derivatives could form 1:1 ICs.The preparation method of ICs,the process of determination of encapsulation efficiency(EE)and loading efficiency(LE)were investigated by pre-experiments.The ultrasonic method was selected and the EE,LE and solubility(S)were used as evaluation indexes to determine the optimal preparation process of ICs.Under the optimal conditions,the EE of CM-β-CD/FP ICs obtained was 58.31%,the LE was 6.52%,and the S was 279.80μg/m L;the EE of CM-HP-β-CD/FP ICs obtained was 81.67%,the LE was 9.33%,and the S was 214.16μg/m L obtained.The prepared ICs were characterized by ultraviolet-visible spectroscopy(UV-Vis),FT-IR,~1H NMR and powder X-ray diffraction(PXRD).(3)The prepared ICs were interacted with chitosan(CS)via electrostatic interacti-ons to form drug-loaded nanoparticles(NPs):CS/CM-β-CD/FP NPs and CS/CM-HP-β-CD/FP NPs.The optimal preparation process of blank NPs was determined by ionic gel method with particle size,polydispersity index(PDI)and Zeta potential as evaluation indexes.On this basis,EE and LE were used as evaluation indicators to determine the best preparation process for drug-loaded NPs.The EE of the prepared CS/CM-β-CD/FP NPs was 90.42%,and the LE was 2.89%,the EE of CS/CM-HP-β-CD/FP NPs was74.23%and the LE of 5.67%.The particle sizes of the blank and drug-loaded NPs were less than 350 nm,the PDI values were less than 0.15,the Zeta potential distribution was in the range of 11.7～16.6 m V,and the NPs were regular spherical with uniform distribution as determined by dynamic light scattering analysis(DLS)and transmission electron microscopy(TEM);and the NPs were characterized by FT-IR.(4)The solubility of ICs,storage stability of drug-loaded NPs and the photostability,in vitro release behavior,insecticidal activity and bee toxicity of both were investigated.The solubility of FP was increased by 102.34 and 76.29 times by CM-β-CD and CM-HP-β-CD encapsulation,respectively.The stability of blank and drug-loaded NPs was better at 4°C and 25°C,and the increase in particle size within 14 d was less than 30 nm,and the retention rate of active ingredients of the drug-loaded NPs was greater than 92%.The stability to light increased significantly,and the drug-loaded NPs showed higher photostability than ICs;ICs were released rapidly in vitro,and drug-loaded NPs had good slowly release performance and pH sensitivity,and released the drug by Fickian diffusion mechanism;Both ICs and drug-laden NPs improved the insecticidal activity of FP,reduced toxicity to honey bees,and improved bioavailability and safety.