Nanogel drug-loading system based on polyvinyl alcohol as well as preparation method and application of nanogel drug-loading system

Abstract

The invention relates to the technical field of pesticide preparations, in particular to a nanogel drug delivery system based on polyvinyl alcohol as well as a preparation method and application of the nanogel drug delivery system. The preparation method of the nanogel drug-loading system comprises the steps that a water phase containing polyvinyl alcohol and an oil phase containing a drug, modified epoxidized soybean oil and an emulsifier are emulsified, the nanogel drug-loading system is obtained, and the modified epoxidized soybean oil is obtained by modifying epoxidized soybean oil through an amino boric acid compound. The nanogel drug-loading system disclosed by the invention can realize pH-responsive and active oxygen-responsive release, and also has hydrophobic leaf surface wettability and excellent rain wash resistance, ultraviolet light stability and environmental safety.

Description

Technical Field

[0001] The present invention relates to the technical field of pesticide preparations, and in particular to a polyvinyl alcohol-based nanogel drug-carrying system, a preparation method thereof, and an application thereof. Background Art

[0002] Pesticides are crucial inputs for ensuring crop yield and quality. However, traditional pesticide formulations suffer from low active ingredient utilization, poor leaf adhesion, and susceptibility to rainwater and UV degradation. These issues lead to significant pesticide loss into the environment, causing water pollution, soil residues, and non-target organism toxicity. In recent years, nanopesticide technology has provided new approaches for enhancing targeted pesticide deposition and controlled release by reducing the particle size of drug delivery systems, manipulating interfacial properties, and introducing stimuli-responsive mechanisms. Among these, nanogel drug delivery systems have become a research hotspot due to their three-dimensional network structure, high drug loading capacity, and environmentally responsive properties.

[0003] Although the current mainstream oil-in-water nanopesticide formulations can reduce the use of organic solvents, they still face the following technical bottlenecks: (1) Insufficient interfacial stability: Conventional emulsifiers have difficulty in building a stable cross-linked network at the oil-water interface, resulting in easy aggregation or disintegration of nanoparticles; (2) Single function: Existing systems mostly rely on a single stimulus response mechanism (such as pH or temperature) and cannot adapt to the multiple regulation requirements of complex field environments; (3) Environmental compatibility defects: Synthetic polymer carriers have poor degradability, and residual components may pose long-term risks to ecological safety. In response to the above problems, some researchers have tried to use natural polymers or degradable polymers to construct nanocarriers, but their hydrophobic drug encapsulation efficiency is low, the process is complex, and the cost is high.

[0004] Epoxidized soybean oil, a non-toxic, renewable plant oil derivative, possesses abundant epoxy groups and excellent biocompatibility. However, when used directly as a crosslinker, it struggles to form stable interfacial crosslinks with hydrophilic polymers. Aminoboronic acid compounds, due to their boronic acid groups and amino reactive sites, can form dynamic boronate bonds with the hydroxyl groups of polyvinyl alcohol. However, their poor solubility in oil phases limits their application in oil-in-water systems. Therefore, the question of how to organically combine these materials to develop a novel multifunctional nanogel drug delivery system remains a pressing issue. Summary of the Invention

[0005] The present invention aims to overcome the above-mentioned problems of the prior art by providing a polyvinyl alcohol-based nanogel drug delivery system, its preparation method, and its application. This nanogel drug delivery system can achieve pH-responsive and reactive oxygen species-responsive release, while also exhibiting hydrophobic leaf wettability, excellent rainwater resistance, UV stability, and environmental safety.

[0006] In order to achieve the above-mentioned objectives, the present invention provides, on the one hand, a method for preparing a nanogel drug delivery system, which comprises: emulsifying an aqueous phase containing polyvinyl alcohol with an oil phase containing a drug, modified epoxidized soybean oil and an emulsifier to obtain a nanogel drug delivery system, wherein the modified epoxidized soybean oil is obtained by modifying epoxidized soybean oil with an aminoboric acid compound.

[0007] The second aspect of the present invention provides a nanogel drug delivery system prepared by the above method.

[0008] The third aspect of the present invention provides an application of the above-mentioned nanogel drug-carrying system in pesticide formulations.

[0009] The present invention uses epoxidized soybean oil modified with aminoboronic acid compounds as an oil-phase crosslinking agent to form a nanoscale gel network through an interfacial crosslinking reaction with a polyvinyl alcohol aqueous phase, resulting in a multifunctional nanogel drug delivery system. The advantages of the nanogel drug delivery system of the present invention are as follows:

[0010] (1) Excellent interfacial cross-linking efficiency: The hydrophobic long chains of epoxidized soybean oil modified with aminoboronic acid compounds can be anchored in the oil phase, and the surface boric acid groups can undergo interfacial cross-linking with the hydroxyl groups of polyethylene glycol to form a stable nanogel network.

[0011] (2) Multi-responsive drug release: The dynamic boron ester bond can be reversibly broken in an acidic or highly reactive oxygen environment, triggering the on-demand release of pesticides.

[0012] (3) Good environmental friendliness and biocompatibility: Epoxidized soybean oil and polyvinyl alcohol are both biodegradable materials, and the super-wetting properties (≤30°) of the nanogel surface can increase the wetting and spreading of pesticides in the liquid, combined with low toxicity to non-target organisms, significantly reducing ecological risks.

[0013] (4) Extremely strong stability: By adjusting the shearing process and component ratio, the nanogel particle size is controlled at 100-300nm, which has both high leaf permeability and resistance to rain erosion. At the same time, the photostability of epoxidized soybean oil is utilized to extend the half-life of the pesticide under ultraviolet irradiation by 2-5 times. DETAILED DESCRIPTION

[0014] The endpoints of the ranges and any values disclosed herein are not limited to the precise ranges or values, and these ranges or values should be understood to include values close to these ranges or values. For numerical ranges, the endpoints of each range, the endpoints of each range and individual point values, and the individual point values can be combined with each other to obtain one or more new numerical ranges, which should be considered to be specifically disclosed herein.

[0015] In order to achieve the above-mentioned objectives, the present invention provides, on the one hand, a method for preparing a nanogel drug delivery system, which comprises: emulsifying an aqueous phase containing polyvinyl alcohol with an oil phase containing a drug, modified epoxidized soybean oil and an emulsifier to obtain a nanogel drug delivery system, wherein the modified epoxidized soybean oil is obtained by modifying epoxidized soybean oil with an aminoboric acid compound.

[0016] According to the present invention, the particle size of the nanogel drug delivery system can be controlled within a certain range by adjusting the preparation process. In order to obtain better performance, preferably, the particle size of the nanogel drug delivery system is 50-400nm, preferably 100-300nm, for example, it can be 120nm, 180nm, 220nm, 270nm and 300nm and the range between any values.

[0017] According to the present invention, in order to enhance the efficiency of the interfacial cross-linking reaction and obtain a better nanogel drug delivery system, preferably, the molecular weight of the polyvinyl alcohol is 10,000-150,000 g / mol, preferably 50,000-100,000 g / mol, for example, it can be 50,000 g / mol, 70,000 g / mol, 90,000 g / mol and 100,000 g / mol and any value thereof.

[0018] According to the present invention, in order to better carry out the cross-linking reaction, preferably, the content of the polyvinyl alcohol in the aqueous phase is 0.2-8wt%, preferably 0.5-5wt%, for example, it can be 0.5wt%, 1wt%, 2wt%, 4wt% and 5wt% and the range between any values thereof.

[0019] According to the present invention, the preparation process of the aqueous phase may include, for example, adding the polyvinyl alcohol into water, and stirring and dissolving the polyvinyl alcohol to obtain the aqueous phase.

[0020] According to the present invention, in order to improve the utilization rate of pesticides, preferably, the content of the drug in the oil phase is 5-50wt%, preferably 10-40wt%, for example, it can be 10wt%, 20wt%, 30wt% and 40wt% and any range between the values.

[0021] According to the present invention, in order to obtain a nanogel drug delivery system with better properties and performance, preferably, the content of the modified epoxidized soybean oil in the oil phase is 10-60wt%, preferably 20-50wt%, for example, it can be 20wt%, 30wt%, 35wt%, 45wt% and 50wt% and the range of any values therebetween.

[0022] According to the present invention, in order to better carry out the emulsification treatment, preferably, the content of the emulsifier in the oil phase is 1-20wt%, preferably 2-10wt%, for example, it can be 2wt%, 5wt%, 6wt%, 8wt% and 10wt% and the range between any values thereof.

[0023] According to the present invention, in order to achieve better emulsification effect, preferably, the solvent of the oil phase is selected from one or more of xylene, cyclohexanone, dichloromethane, n-hexane, n-heptane and ethyl acetate, preferably one or more of cyclohexanone, n-hexane and xylene.

[0024] According to the present invention, in order to achieve better synergy with polyvinyl alcohol, preferably, the preparation method of the modified epoxidized soybean oil includes: contacting and reacting the aminoboric acid compound with the epoxidized soybean oil to obtain the modified epoxidized soybean oil.

[0025] Preferably, the aminoboronic acid compound is selected from one or more of 3-aminophenylboronic acid, 4-(diphenylamino)phenylboronic acid, 4-aminophenylboronic acid and 2-aminophenylboronic acid, preferably 3-aminophenylboronic acid and / or 4-aminophenylboronic acid.

[0026] Preferably, the molar ratio of the epoxidized soybean oil to the aminoboric acid compound is 1:1-15, preferably 1:1-10, for example, it can be 1:2, 1:5, 1:8, 1:10 and any range therebetween.

[0027] Preferably, the solvent for the contact reaction is selected from one or more of xylene, cyclohexanone, dichloromethane, n-hexane, n-heptane and ethyl acetate, preferably one or more of dichloromethane, xylene and cyclohexanone.

[0028] Preferably, the amount of the solvent used in the contact reaction is 5-30 mL, preferably 5-15 mL, relative to 1 mmol of the aminoboronic acid compound, for example, 5 mL, 8 mL, 10 mL, 12 mL, and any range therebetween.

[0029] According to the present invention, in order to better carry out the contact reaction, preferably, the conditions of the contact reaction include: a temperature of 10-40°C and a time of 10-30h; more preferably, the conditions of the contact reaction include: a temperature of 20-30°C (for example, it can be a range of values such as 20°C, 25°C, 28°C and 30°C and any values therebetween), and a time of 10-20h (for example, it can be a range of values such as 10h, 12h, 15h and 18h and any values therebetween).

[0030] According to the present invention, in order to enhance the effect of the cross-linking reaction, preferably, the emulsifier is selected from one or more of the Span series, Tween series and polyoxyethylene ether nonionic surfactants, preferably one or more of Span-80, Tween-20, Tween-60, Tween-80 and polyoxyethylene ether.

[0031] According to the present invention, the drug can be selected from a wide range. In order to achieve better effects and improve the utilization rate of pesticides, preferably, the drug is selected from one or more of fungicides, herbicides, insecticides and acaricides and antiviral agents, preferably one or more of pyraclostrobin, azoxystrobin, tebuconazole, difenoconazole, atrazine, mesotrione, avermectin, imidacloprid, bifenthrin and ningnanmycin.

[0032] According to the present invention, the preparation process of the oil phase may include, for example, adding the drug, the modified epoxidized soybean oil and the emulsifier into a solvent, and stirring and dissolving them to obtain the oil phase.

[0033] According to the present invention, in order to obtain a better nanogel drug delivery system, preferably, the weight ratio of the oil phase to the aqueous phase is 1:1-20, preferably 1:5-15, for example, it can be 1:5, 1:8, 1:12 and 1:15 and any range therebetween.

[0034] Preferably, the shear rate of the emulsification treatment is 8000-25000 rpm, preferably 10000-20000 rpm, for example, it can be 10000 rpm, 15000 rpm, 18000 rpm, 20000 rpm and any range therebetween.

[0035] Preferably, the emulsification treatment time is 2-40 min, preferably 5-25 min, for example, it can be 5 min, 10 min, 15 min, 20 min, 25 min and any value thereof.

[0036] The second aspect of the present invention provides a nanogel drug delivery system prepared by the above method.

[0037] The third aspect of the present invention provides an application of the above-mentioned nanogel drug-carrying system in pesticide formulations.

[0038] The present invention uses epoxidized soybean oil modified with aminoboronic acid compounds as an oil-phase crosslinker, which reacts with polyvinyl alcohol (PVA) in an aqueous phase to construct a nanoscale gel network, resulting in a multifunctional nanogel drug delivery system. This nanogel drug delivery system achieves pH-responsive and reactive oxygen species-responsive release, while also exhibiting hydrophobic leaf wettability, excellent rainwater resistance, UV stability, and environmental safety.

[0039] The present invention will be described in detail below through examples.

[0040] In the following examples, the devices used are all conventional experimental devices in this field, the experimental operations adopted are all conventional operations in this field, and the raw materials, reagents, etc. used can be obtained commercially.

[0041] Epoxidized soybean oil, polyvinyl alcohol (molecular weight, 80,000 g / mol), and tebuconazole were purchased from Beijing Inokai. Abamectin, azoxystrobin, atrazine, and imidacloprid were purchased from Xiens Biochemical Technology. Span-80, Tween-80, and Tween-60 were purchased from Shanghai Myrel Biochemical Technology. Tween-20 and polyoxyethylene ether (molecular weight, 2000 g / mol) were purchased from Shanghai Bid Pharmaceutical.

[0042] Example 1

[0043] (1) Epoxidized soybean oil and 3-aminophenylboronic acid were added to xylene in a molar ratio of 1:2 and reacted at 25°C for 10 h to obtain 3-aminophenylboronic acid-modified epoxidized soybean oil, wherein the amount of xylene used was 5 mL relative to 1 mmol of 3-aminophenylboronic acid.

[0044] (2) Prepare a 3 wt% polyvinyl alcohol aqueous solution as the aqueous phase.

[0045] (3) Prepare an oil phase with a content of 30 wt% of avermectin, a content of 35 wt% of 3-aminophenylboronic acid modified epoxy soybean oil, a content of 5 wt% of Span-80, and the balance being solvent xylene.

[0046] (4) The oil phase was slowly added to the water phase (the weight ratio of the oil phase to the water phase was 1:5), and emulsified at a shear rate of 15,000 rpm for 5 min to obtain a nanogel drug delivery system.

[0047] Example 2

[0048] (1) Epoxidized soybean oil and 3-aminophenylboronic acid were added to cyclohexanone in a molar ratio of 1:4, and the mixture was reacted at 25°C for 12 h to obtain 3-aminophenylboronic acid-modified epoxidized soybean oil. The amount of cyclohexanone used was 8 mL relative to 1 mmol of 3-aminophenylboronic acid.

[0049] (2) Prepare a 0.5 wt% polyvinyl alcohol aqueous solution as the aqueous phase.

[0050] (3) An oil phase was prepared with azoxystrobin content of 15 wt%, 3-aminophenylboronic acid modified epoxy soybean oil content of 45 wt%, Tween-20 content of 4 wt%, and the balance being solvent cyclohexanone.

[0051] (4) The oil phase was slowly added to the water phase (the weight ratio of the oil phase to the water phase was 1:8), and emulsified at a shear rate of 12000 rpm for 8 min to obtain a nanogel drug delivery system.

[0052] Example 3

[0053] (1) Epoxidized soybean oil and 3-aminophenylboronic acid were added to n-hexane at a molar ratio of 1:6 and reacted at 25°C for 10 h to obtain 3-aminophenylboronic acid-modified epoxidized soybean oil, wherein the amount of n-hexane used was 10 mL relative to 1 mmol of 3-aminophenylboronic acid.

[0054] (2) Prepare a 5 wt% polyvinyl alcohol aqueous solution as the aqueous phase.

[0055] (3) Prepare an oil phase with a content of 40 wt% of atrazine, a content of 25 wt% of 3-aminophenylboronic acid modified epoxy soybean oil, a content of 6 wt% of a Tween-80 / Span-80 mixed emulsifier (the weight ratio of Tween-80 to Span-80 is 1:1), and the balance being a solvent n-hexane.

[0056] (4) The oil phase was slowly added to the water phase (the weight ratio of the oil phase to the water phase was 1:10), and emulsified at a shear rate of 20,000 rpm for 12 min to obtain a nanogel drug delivery system.

[0057] Example 4

[0058] (1) Epoxidized soybean oil and 3-aminophenylboronic acid were added to xylene in a molar ratio of 1:10 and reacted at 25°C for 12 h to obtain 3-aminophenylboronic acid-modified epoxidized soybean oil, wherein the amount of xylene used was 15 mL relative to 1 mmol of 3-aminophenylboronic acid.

[0059] (2) Prepare a 3.5 wt% polyvinyl alcohol aqueous solution as the aqueous phase.

[0060] (3) Prepare an oil phase with an imidacloprid content of 20 wt%, a tebuconazole content of 15 wt%, a 3-aminophenylboronic acid modified epoxy soybean oil content of 30 wt%, a Tween-60 content of 3 wt%, and the balance being solvent xylene.

[0061] (4) The oil phase was slowly added to the water phase (the weight ratio of the oil phase to the water phase was 1:12.5), and emulsified at a shear rate of 20,000 rpm for 15 min to obtain a nanogel drug delivery system.

[0062] Example 5

[0063] The method of Example 1 is different in that, in step (3), Span-80 is replaced by polyoxyethylene ether.

[0064] Example 6

[0065] The method of Example 1 is different in that, in step (3), the content of 3-aminophenylboronic acid modified epoxidized soybean oil is 10 wt%.

[0066] Example 7

[0067] The method of Example 1 is different in that, in step (3), the content of 3-aminophenylboronic acid modified epoxy soybean oil is 60 wt%.

[0068] Example 8

[0069] The method of Example 1 is different in that, in step (2), the concentration of the polyvinyl alcohol aqueous solution is 0.2 wt %.

[0070] Example 9

[0071] The method of Example 1 is different in that, in step (2), the concentration of the polyvinyl alcohol aqueous solution is 8 wt %.

[0072] Example 10

[0073] The method of Example 1 is different in that, in step (1), 3-aminophenylboronic acid is replaced by 2-aminophenylboronic acid.

[0074] Example 11

[0075] The method of Example 1 is different in that in step (1), 3-aminophenylboronic acid is replaced by 4-(diphenylamino)phenylboronic acid.

[0076] Comparative Example 1

[0077] The method of Example 1 is different in that step (1) is not included and the 3-aminophenylboronic acid-modified epoxidized soybean oil in step (3) is replaced by epoxidized soybean oil.

[0078] Comparative Example 2

[0079] The method of Example 1 is the same, except that the 3 wt % polyvinyl alcohol aqueous solution in step (2) is replaced by deionized water as the aqueous phase.

[0080] Test Example 1

[0081] Encapsulation efficiency: The encapsulation efficiency of the nanogel drug delivery system was tested by high performance liquid chromatography.

[0082] Particle size: The particle size of the nanogel drug delivery system was measured by Mastersizer 3000 laser particle size analyzer.

[0083] Wettability: The leaf contact angle of the nanogel drug delivery system was tested using an OCA25 optical contact angle meter.

[0084] UV resistance: The half-life of the drug in the nanogel drug delivery system was tested by high performance liquid chromatography to reflect the UV resistance of the nanogel drug delivery system.

[0085] Anti-scouring property: The drug was washed under 10 mL / min simulated rainfall for 4 min, and the drug residual rate in the nanogel drug delivery system was tested by high performance liquid chromatography.

[0086] The test results are shown in Table 1.

[0087] Table 1

[0088]

[0089] Test Example 2

[0090] pH / ROS (pH / reactive oxygen species) responsiveness: The pH / ROS responsiveness of the nanogel drug delivery system was tested by high performance liquid chromatography.

[0091] Ecotoxicity: 130 rice seeds were evenly spread in a 10cm circular culture medium and soaked in a 100mg / L preparation solution. A sterile water treatment group was set as a control. The rice seed germination rate was calculated after 4 days. 8 zebrafish were placed in 2L solutions of different preparation concentrations. Pure water was set as a blank control group. After 96 hours, the median lethal concentration (96h LC) of zebrafish was 0.05. 50 The drug solution of different concentrations was applied to the mesothorax of bees by drip method, and the mortality rate within 48 hours was observed and the median lethal dose (LD50) was calculated. 50 ). The ecotoxicity of the nanogel drug delivery system to rice, zebrafish and honeybees was tested.

[0092] The test results are shown in Table 2.

[0093] Table 2

[0094]

[0095] As can be seen from Tables 1 and 2, the nanogel drug delivery systems obtained using Examples 1-11 of the present invention exhibit high encapsulation efficiency, good wettability, UV resistance, and rainwater resistance, as well as excellent pH / ROS responsiveness and ecocompatibility. The performance of the nanogel drug delivery systems obtained in Examples 1-11 is significantly superior to that of Comparative Examples 1-2.

[0096] Test Example 3

[0097] Verification of extreme pH response: The nanogel drug delivery system prepared in Example 1 was tested under strongly acidic conditions of pH 4. A certain amount of the test suspension was placed in a dialysis bag, 5 mL of dialysis medium was added, and the suspension was placed in 195 mL for simulated release. At regular intervals, 1 mL of the suspension was sampled and measured for concentration using high-performance liquid chromatography. The test results showed that the nanogel drug delivery system exhibited a burst release rate of 60% by weight within 2 hours, compared to only 10% by weight under neutral conditions. This characteristic is suitable for controlling crop root diseases in acidic soils, achieving localized, high-concentration, targeted drug release.

[0098] Test Example 4

[0099] Ecotoxicity test expansion: The nanogel drug delivery system prepared in Example 1 was subjected to a biosafety test according to the method of GB / T 31270.15. The test results showed that the toxicity of the nanogel drug delivery system to earthworms was LC 50 >100mg / kg, EC inhibition on algae growth 50 >100mg / L, significantly better than traditional emulsifiable concentrate preparations (avermectin emulsifiable concentrate preparations, purchased from Xiens Biochemical Technology, EC 50 =15mg / L).

[0100] Test Example 5

[0101] Field simulated UV aging: The nanogel drug delivery system prepared in Example 2 was subjected to a 30-day simulated aging experiment under natural light. Samples were taken regularly for high-performance liquid chromatography analysis. The test results showed that the degradation rate of myclobutanil in the nanogel drug delivery system was 28 wt%, while the degradation rate of conventional myclobutanil suspension (purchased from Xiens Biochemical Technology) was 65 wt%.

[0102] Test Example 6

[0103] Scale-up production verification: Following the method of Example 1, scale-up production was carried out in a 50 L reactor. The batch size variation was controlled within ±15 nm, and the encapsulation efficiency was stable at >93 wt%. Large-scale production verified the process repeatability and laid the foundation for industrial application.

[0104] The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, various simple variations of the technical solution of the present invention may be made, including combining the various technical features in any other appropriate manner. These simple variations and combinations should also be regarded as disclosed in the present invention and fall within the scope of protection of the present invention.

Claims

1. A method for preparing a nanogel drug delivery system, characterized in that: The method comprises: emulsifying an aqueous phase containing polyvinyl alcohol with an oil phase containing a drug, modified epoxidized soybean oil and an emulsifier to obtain a nanogel drug-carrying system, wherein the modified epoxidized soybean oil is obtained by modifying epoxidized soybean oil with an aminoboric acid compound.

2. The method according to claim 1, wherein The particle size of the nanogel drug delivery system is 50-400 nm, preferably 100-300 nm; and / or, the molecular weight of the polyvinyl alcohol is 10,000-150,000 g / mol, preferably 50,000-100,000 g / mol; And / or, the content of the polyvinyl alcohol in the aqueous phase is 0.2-8 wt%, preferably 0.5-5 wt%.

3. The method according to claim 1 or 2, wherein The content of the drug in the oil phase is 5-50wt%, preferably 10-40wt%; And / or, the content of the modified epoxidized soybean oil in the oil phase is 10-60wt%, preferably 20-50wt%; And / or, the content of the emulsifier in the oil phase is 1-20 wt%, preferably 2-10 wt%.

4. The method according to any one of claims 1 to 3, wherein: The solvent of the oil phase is selected from one or more of xylene, cyclohexanone, dichloromethane, n-hexane, n-heptane and ethyl acetate, preferably one or more of cyclohexanone, n-hexane and xylene.

5. The method according to any one of claims 1 to 4, wherein: The preparation method of the modified epoxidized soybean oil comprises: contacting and reacting the aminoboric acid compound with the epoxidized soybean oil to obtain the modified epoxidized soybean oil; Preferably, the aminoboronic acid compound is selected from one or more of 3-aminophenylboronic acid, 4-(diphenylamino)phenylboronic acid, 4-aminophenylboronic acid and 2-aminophenylboronic acid, preferably 3-aminophenylboronic acid and / or 4-aminophenylboronic acid; Preferably, the molar ratio of the epoxidized soybean oil to the aminoboric acid compound is 1:1-15, preferably 1:1-10; Preferably, the solvent for the contact reaction is selected from one or more of xylene, cyclohexanone, dichloromethane, n-hexane, n-heptane and ethyl acetate, preferably one or more of dichloromethane, xylene and cyclohexanone; Preferably, the amount of the solvent used in the contact reaction is 5-30 mL, preferably 5-15 mL, relative to 1 mmol of the aminoboronic acid compound; Preferably, the conditions for the contact reaction include: temperature of 10-40° C., and time of 10-30 h; more preferably, the conditions for the contact reaction include: temperature of 20-30° C., and time of 10-20 h.

6. The method according to any one of claims 1 to 5, wherein: The emulsifier is selected from one or more of Span series, Tween series and polyoxyethylene ether nonionic surfactants, preferably one or more of Span-80, Tween-20, Tween-60, Tween-80 and polyoxyethylene ether.

7. The method according to any one of claims 1 to 6, wherein: The drug is selected from one or more of fungicides, herbicides, insecticides and acaricides and antiviral agents, preferably one or more of pyraclostrobin, azoxystrobin, tebuconazole, difenoconazole, atrazine, mesotrione, avermectin, imidacloprid, bifenthrin and ningnanmycin.

8. The method according to any one of claims 1 to 7, wherein: The weight ratio of the oil phase to the water phase is 1:1-20, preferably 1:5-15; and / or, the shear rate of the emulsification treatment is 8000-25000 rpm, preferably 10000-20000 rpm; And / or, the emulsification treatment time is 2-40 min, preferably 5-25 min.

9. The nanogel drug delivery system prepared by the method according to any one of claims 1 to 8.

10. Use of the nanogel drug delivery system according to claim 9 in pesticide preparations.

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