CN115558038A - Preparation of dopamine functionalized alginic acid derivative and stable drug-loaded emulsion thereof - Google Patents
Preparation of dopamine functionalized alginic acid derivative and stable drug-loaded emulsion thereof Download PDFInfo
- Publication number
- CN115558038A CN115558038A CN202211015317.3A CN202211015317A CN115558038A CN 115558038 A CN115558038 A CN 115558038A CN 202211015317 A CN202211015317 A CN 202211015317A CN 115558038 A CN115558038 A CN 115558038A
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- Prior art keywords
- alg
- dopamine
- emulsion
- functionalized
- alginic acid
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Links
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- 235000010443 alginic acid Nutrition 0.000 title claims abstract description 44
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Images
Classifications
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- C—CHEMISTRY; METALLURGY
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- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
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- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0084—Guluromannuronans, e.g. alginic acid, i.e. D-mannuronic acid and D-guluronic acid units linked with alternating alpha- and beta-1,4-glycosidic bonds; Derivatives thereof, e.g. alginates
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- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/02—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing liquids as carriers, diluents or solvents
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- A—HUMAN NECESSITIES
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- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/08—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing solids as carriers or diluents
- A01N25/10—Macromolecular compounds
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- A—HUMAN NECESSITIES
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- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
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- A—HUMAN NECESSITIES
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Abstract
The invention provides a preparation method of dopamine functionalized alginic acid derivatives (Alg-DA-x) and a stable drug-loaded emulsion thereof. The Alg-DA-x provided by the invention has excellent ultraviolet shielding performance, adhesion and retention performance, and the stable emulsion also has good emulsion stability, ultraviolet shielding performance, rheological property, adhesion and retention performance, has excellent encapsulation capacity on the medicine, and can stably and slowly release the medicine. For example, AVM serving as a model drug is encapsulated into an emulsion prepared by Alg-DA-x, the encapsulation rate of the AVM can reach 85.27 percent, the AVM can be slowly released in a release period, the highest drug residue rate can reach 73.55 percent after being irradiated by an ultraviolet lamp for 48 hours, the maximum wetting diameter can reach 0.790mm when the surface of a blade is irradiated for 300s, and the minimum dynamic contact angle can reach 45.21 degrees. The Alg-DA-x provided by the invention is expected to be used as a multifunctional drug carrier and applied to the field of drug delivery.
Description
Technical Field
The invention relates to an alginic acid derivative, in particular to a preparation method of a dopamine functionalized alginic acid derivative and a stable drug-loaded emulsion thereof.
Background
The pesticide is used as a chemical preparation, and the reasonable use can effectively repel, kill or inhibit the reproduction and growth of pests in other ways, thereby achieving the purposes of protecting crops from diseases and insect pests and improving the yield. In the modern agricultural production process, pesticides play a vital role. However, most pesticide formulations do not wet and adhere well to the surface of the crop leaves during use, resulting in poor control of pests by the drug and severe loss of agricultural and economic benefits.
The effective deposition and retention of the medicine liquid drops on the surface of the material have important scientific significance for agriculture. For agricultural sprays, effective wetting and spreading of spray droplets on the surface of crop leaves is the key to improving pesticide utilization and alleviating environmental pollution. Some studies have shown that the leaf surface of crops has a waxy layer formed by alkanes, flavonoids and other substances. It has been reported that the more long-chain hydrocarbons the waxy layer contains, the more difficult it is for the droplets to wet and spread on the plant surface. It is a common effective means of controlling agricultural pests by spraying pesticidal sprays onto the surface of crops. However, many crop surfaces are difficult to deposit and retain effectively with aqueous pesticidal spray droplets due to the hydrophobic nature of the structure or the attachment of hydrophobic substances such as waxy layers to the surface. Furthermore, due to the short contact time of the droplets during spraying, the impinging droplets typically bounce off the flat superhydrophobic surface within 10 ms. This splashing action of the droplets often results in the droplets of pesticide rolling off the surface of the plant to the ground and causing serious pesticide accumulation problems. The most significant effect is the diffusion of accumulated drugs which causes contamination of soil, surface water and groundwater. In order to increase the efficiency of pesticide utilization and reduce the pollution of pesticide residues to soil and water sources, it becomes important to use certain additives to improve the deposition and retention properties of the droplets.
Sodium alginate, as a natural high-molecular polysaccharide polymer, has the characteristics of no toxicity, biocompatibility and biodegradability, and has wide application in the field of drug delivery. However, the application of pure sodium alginate in agriculture is limited by the defects of strong hydrophilicity, poor adhesion on the surface of plant leaves and the like.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provides a dopamine functionalized alginic acid derivative, a stable drug-loaded emulsion and a preparation method thereof.
The invention provides a dopamine functionalized alginic acid derivative, which is characterized by being a mixture of compounds shown in a structural formula (1) and a structural formula (2),
preferably, the dopamine-functionalized alginic acid derivative is prepared by oxidative polymerization of dopamine-functionalized sodium alginate represented by structural formula (3):
preferably, the oxidative polymerization reaction occurs at an ambient pH of 5.3 or more, preferably at a pH of 6.8 or more, more preferably at a pH of 7 or more, even more preferably at a pH of 8.3 or more, and even more preferably at a pH of 9.8 or more.
Preferably, the weight average molecular weight of the dopamine functionalized alginic acid derivative is not less than 60000, preferably 600000-1200000, such as 650000, 700000, 750000, 800000, 803596, 850000, 863236, 900000, 942563, 950000, 1000000, 1041451, 1100000, 1200000, and the like.
In a second aspect of the present invention, there is provided a method for preparing a dopamine-functionalized alginic acid derivative according to the first aspect of the present invention, comprising the steps of: (1) Fully activating carboxyl of sodium alginate by 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC & HCl) and N-hydroxysuccinimide (NHS), adding dopamine hydrochloride, and fully reacting to obtain dopamine-functionalized sodium alginate; (2) And carrying out oxidative polymerization on the obtained dopamine-functionalized sodium alginate to obtain the dopamine-functionalized alginic acid derivative.
Preferably, the oxidative polymerization reaction occurs at an ambient pH of 5.3 or more, preferably at a pH of 6.8 or more, more preferably at a pH of 7 or more, even more preferably at a pH of 8.3 or more, and even more preferably at a pH of 9.8 or more.
In a third aspect of the present invention, an emulsion is provided, wherein the emulsion comprises an oil phase and a water phase, and the dopamine-functionalized alginic acid derivative according to the first aspect of the present invention or the dopamine-functionalized alginic acid derivative prepared by the preparation method according to the second aspect of the present invention is used as a stabilizer.
Wherein the volume ratio of the oil phase to the aqueous phase is 1: 0.1 to 10, such as 1: 0.2, 1: 0.3, 1: 0.4, 1: 0.5, 1: 0.6, 1: 0.7, 1: 0.8, 1: 0.9, 1:1, 1: 2, 1: 3, 1: 4, 1: 5, 1: 6, 1: 7, 1: 8, 1: 9, or 1:10, etc.
Wherein the concentration of the dopamine-functionalized alginic acid derivative in the aqueous phase is 0.1-10g/L, such as 0.1g/L, 0.2g/L, 0.3g/L, 0.4g/L, 0.5g/L, 0.6g/L, 0.7g/L, 0.8g/L, 0.9g/L, 1g/L, 1.5g/L, 2g/L, 2.5g/L, 3g/L, 4g/L, 5g/L, 6g/L, 7g/L, 8g/L, 9g/L, or 10g/L. Preferably the concentration of the dopamine-functionalized alginic acid derivative in the aqueous phase is 0.5 to 2.5g/L.
Wherein, the oil phase comprises a solvent which is not miscible with water or slightly soluble in water, and the solvent is preferably any one or a mixture of at least two of silicone oil, fatty esters, aromatic hydrocarbons, alkanes and alcohols with the chain length of 6-16, and petroleum hydrocarbons with the chain length of 22-50, and is more preferably any one or a mixture of at least two of fatty esters, alkanes with the chain length of 6-16, and alcohols.
The oil phase may be a common oil phase used for preparing an emulsion, and the present invention is not particularly limited thereto, and may be appropriately selected by those skilled in the art according to the needs of the actual application. Preferably, the oil phase may consist of only water-immiscible or sparingly water-soluble solvents, and preferably, the oil phase may contain other soluble substances selected from any one or a mixture of at least two of fat-soluble drugs, fat-soluble markers, fat-soluble enzymes, or fat-soluble proteins.
Wherein, the aqueous phase can be the aqueous phase commonly used for preparing emulsions, the invention is not limited in particular, and those skilled in the art can select the aqueous phase according to the needs of practical application. Preferably, the aqueous phase comprises any one of water, phosphate buffer, acetate buffer, citrate buffer or Tris buffer, or a mixture of at least two of them.
Preferably, the water phase also comprises other water-soluble substances, and the water-soluble substances are any one or a mixture of at least two of salts, antibodies, protein polypeptide drugs and enzymes, cytokines or saccharides. The salt substances are sodium chloride, sodium acetate, potassium chloride, calcium chloride and the like.
Dissolving or dispersing the dopamine functional alginic acid derivative according to the first aspect of the present invention or the dopamine functional alginic acid derivative prepared by the preparation method according to the second aspect of the present invention in a water phase, adding an oil phase, and performing high-speed shearing to obtain the emulsion according to the third aspect of the present invention.
The fourth aspect of the present invention provides a drug-loaded emulsion, wherein the drug-loaded emulsion comprises an oil phase and an aqueous phase, the dopamine functional alginic acid derivative according to the first aspect of the present invention or the dopamine functional alginic acid derivative prepared by the preparation method according to the second aspect of the present invention is used as a stabilizer, and a drug is dissolved in the oil phase or the aqueous phase.
Wherein, the medicament can be selected according to the actual requirement, and the invention does not limit the medicament. In one embodiment of the present invention, where Abamectin (AVM) is used, the oil phase may be liquid paraffin containing abamectin. Wherein, the concentration of avermectin in the liquid paraffin can be adjusted by technicians in the field according to experience and needs, and the invention is not limited. Preferably, the concentration of the abamectin in the liquid paraffin is 1-100mg/ml.
Wherein the volume ratio of the oil phase to the aqueous phase is 1: 0.1 to 10, such as 1: 0.2, 1: 0.3, 1: 0.4, 1: 0.5, 1: 0.6, 1: 0.7, 1: 0.8, 1: 0.9, 1:1, 1: 2, 1: 3, 1: 4, 1: 5, 1: 6, 1: 7, 1: 8, 1: 9, or 1:10, etc.
Wherein the concentration of the dopamine-functionalized alginic acid derivative in the aqueous phase is 0.1-10g/L, such as 0.1g/L, 0.2g/L, 0.3g/L, 0.4g/L, 0.5g/L, 0.6g/L, 0.7g/L, 0.8g/L, 0.9g/L, 1g/L, 1.5g/L, 2g/L, 2.5g/L, 3g/L, 4g/L, 5g/L, 6g/L, 7g/L, 8g/L, 9g/L, or 10g/L. Preferably the concentration of the dopamine-functionalized alginic acid derivative in the aqueous phase is 0.5 to 2.5g/L.
Wherein, the oil phase comprises a solvent which is not miscible with water or slightly soluble in water, and the solvent is preferably any one or a mixture of at least two of silicone oil, fatty esters, aromatic hydrocarbons, alkanes and alcohols with the chain length of 6-16, and petroleum hydrocarbons with the chain length of 22-50, and is more preferably any one or a mixture of at least two of fatty esters, alkanes with the chain length of 6-16, and alcohols.
The oil phase may be a common oil phase used for preparing an emulsion, and the present invention is not particularly limited herein, and may be reasonably selected by one skilled in the art according to the needs of practical applications. Preferably, the oil phase may consist of only water-immiscible or sparingly water-soluble solvents, and preferably, the oil phase may contain other soluble substances selected from any one or a mixture of at least two of fat-soluble drugs, fat-soluble markers, fat-soluble enzymes, or fat-soluble proteins.
Wherein, the aqueous phase can be the aqueous phase commonly used for preparing emulsions, the invention is not limited in particular, and those skilled in the art can select the aqueous phase according to the needs of practical application. Preferably, the aqueous phase comprises any one of water, phosphate buffer, acetate buffer, citrate buffer or Tris buffer, or a mixture of at least two thereof.
Preferably, the water phase also comprises other water-soluble substances, and the water-soluble substances are any one or a mixture of at least two of salts, antibodies, protein polypeptide drugs and enzymes, cytokines or saccharides. The salt substances are sodium chloride, sodium acetate, potassium chloride, calcium chloride and the like.
Dissolving or dispersing the dopamine functional alginic acid derivative of the first aspect of the present invention or the dopamine functional alginic acid derivative prepared by the preparation method of the second aspect of the present invention in a water phase, dissolving a drug in the water phase and/or an oil phase, adding the water phase into the oil phase, and performing high-speed shearing to obtain the drug-loaded emulsion of the fourth aspect of the present invention.
A fifth aspect of the invention provides the use of a dopamine functionalized alginic acid derivative according to the first aspect of the invention or an emulsion according to the third aspect of the invention or a drug loaded emulsion according to the fourth aspect of the invention in the fields of biomedicine, cosmetics, food, petroleum and wastewater treatment.
A sixth aspect of the invention provides the use of a dopamine functionalized alginic acid derivative according to the first aspect of the invention or an emulsion according to the third aspect of the invention or a pre-loaded emulsion according to the fourth aspect of the invention for the preparation of a slow release formulation of a drug.
The dopamine functionalized alginic acid derivative (Alg-DA-x) provided by the invention has excellent ultraviolet shielding property, adhesion and retention property, and the stable emulsion of the derivative also has good emulsion stability, ultraviolet shielding property, rheological property, adhesion and retention property, has excellent encapsulation capacity on the medicine, and can stably and slowly release the medicine. For example, AVM is used as a model drug and is packaged into an emulsion prepared from Alg-DA-x, the encapsulation rate of the AVM can reach 85.27%, the AVM can be slowly released in a release period, the drug residue rate can reach 73.55% at most after the ultraviolet lamp irradiates for 48 hours, the ultraviolet shielding performance is good, the maximum wetting diameter of the blade surface reaches 0.790mm when the blade surface is wetted for 300s, the minimum dynamic contact angle reaches 45.21 degrees, and the blade surface has excellent adhesion and deposition performance. The Alg-DA-x provided by the invention is expected to be used as a multifunctional drug carrier and applied to the field of drug delivery.
Drawings
FIG. 1 is a diagram (b) showing the oxidative polymerization mechanism (a) of Dopamine (DA) under alkaline conditions and the reaction mechanism of Alg-DA-x.
FIG. 2 is a FT-IR spectrum of Alg and Alg-DA-x (a)) And with 1 H NMR spectrum (b).
FIG. 3 shows UV spectrum (a) and TGA spectrum (b) of Alg and Alg-DA-x.
FIG. 4 is a particle size potential diagram (a) and a morphology TEM image (b) of Alg-DA-x self-assembled micelles.
FIG. 5 is a photograph of lamp-irradiated methylene blue dye (a) and content (b), wherein 5.3, 6.8, 8.3, 9.8 in FIG. 5 (a) are respectively Alg-DA-5.3, alg-DA-6.8, alg-DA-8.3 and Alg-DA-9.8.
FIG. 6 is a photograph of Alg-DA-x on the surface of banana leaves (a), surface tension (b), wetting diameter (c) and dynamic contact angle (d).
FIG. 7 shows fluorescence images (a) and fluorescence loss ratios (b) of Alg-DA-x on the surface of banana leaves.
FIG. 8 is a microscope photograph of EAD-x emulsion droplets (a), droplet size distribution (b).
FIG. 9 is a TSI profile (c) and a TSI profile (d) for an EAD-x emulsion.
FIG. 10 is an SEM picture of an Alg-DA-x stabilized styrene emulsion (a); the stability mechanism of the emulsion is shown in (b).
FIG. 11 is an appearance diagram (a) and a height histogram (b) of the emulsion for ultraviolet light irradiation of EAD-x; curve (c) relating apparent viscosity to shear rate of EAD-x; strain sweep curve (d) for EAD-x; dynamic oscillation frequency sweep curve (e) of EAD-x, where the four samples in FIG. 11 (a) are, from left to right, alg-DA-5.3, alg-DA-6.8, alg-DA-8.3, and Alg-DA-9.8.
FIG. 12 is an AVM encapsulation efficiency (a) and cumulative release profile (b) for AVM @ EAD-x.
FIG. 13 is a graph of the residual ratio of AVM after UV irradiation for AVM @ EAD-x.
FIG. 14 is a photograph of deposition of AVM @ EAD-x on the surface of banana leaf (a); AVM @ EAD-x dynamic contact angle (b) and wetting diameter (c) on banana leaf surface.
Detailed Description
The invention will be better understood from the following description of specific embodiments with reference to the accompanying drawings. The examples do not specify particular techniques or conditions, and are performed according to the techniques or conditions described in the literature in the art or according to the product specifications. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products commercially available.
1. preparation and characterization of pH-regulated dopamine-functionalized alginic acid derivative (Alg-DA-x)
(1) Synthesis of Alg-DA-x
The synthesis of 4 pH-adjusted dopamine-functionalized alginic acid derivatives Alg-DA-x is shown in FIG. 1.
Dopamine-functionalized sodium alginate (Alg-DA) was first prepared. The method comprises the following steps: 200mL of a 1wt% sodium alginate solution is prepared and placed in a three-neck flask, the pH value of the solution is adjusted to 3.6 by hydrochloric acid, after sufficient stirring, 9mmol of EDC & HCl and NHS are sequentially added, and the mixture is sufficiently stirred for 3 hours under a nitrogen atmosphere so as to sufficiently activate the carboxyl group of Alg. Then, 9mmol of dopamine hydrochloride (DA) was added to the above solution, and the mixture was sufficiently stirred at room temperature for 24 hours. The reacted solution was dialyzed in a dialysis bag (molecular weight cut-off 3500 Da) for 3 days to remove unreacted small molecular impurities. Finally, alg-DA was obtained by freeze-drying.
Secondly, preparing Alg-DA-x by adjusting alkaline environment. First, 4 bottles of 2g/L Alg-DA solution were prepared with deionized water, and the pH of the solution was adjusted to 5.3, 6.8, 8.3, and 9.8 with NaOH, respectively. After 4 bottles of Alg-DA at different pH were placed at room temperature and stirred well for 4h, dialyzed in dialysis bag for two days to remove NaOH. And finally, carrying out spray drying on the purified solution by using a nano spray dryer B-90. The samples after drying were collected and named Alg-DA-x (Alg-DA-5.3, alg-DA-6.8, alg-DA-8.3, and Alg-DA-9.8). The degree of substitution of Alg-DA was determined to be 27% by measuring the absorbance of Alg-DA at 280nm using a Lambda 750s UV spectrophotometer.
(2) Fourier transform infrared spectroscopy (FT-IR) analysis
Taking a certain amount of Alg and Alg-DA-x to mix with a proper amount of KBr in a fixed ratio (sample: KBr =1 & lt 100 & gt), respectively, grinding the sample and the KBr into powder under the irradiation of an infrared lamp, pressing the powder into transparent sheets by using a tablet press, and setting the scanning range of a Bruker T27 Fourier transform infrared spectrometer to be 500-4000cm -1 And characterizing the sample to analyze the sample for functional group composition and differences.
FT-IR spectra of Alg and Alg-DA-x are shown in FIG. 2 (a). For unmodified Alg,3408cm -1 The absorption peak is O-H stretching vibration peak on Alg and is 2928cm -1 The absorption peaks are C-H stretching vibration peaks on Alg, and are at 1094 and 1033cm -1 The absorption peaks are C-H and C-O-C stretching vibration peaks of Alg, and are at 1613 and 1407cm -1 The characteristic peaks at (a) are respectively assigned to the asymmetric and symmetric stretching vibration peaks of-COO-of Alg (Islam et al, 2010). Compared with Alg, alg-DA-x is at 1733,1532 and 1280cm -1 New absorption peak appears at the position, wherein 1733cm -1 C = O stretching vibration, 1532 and 1280cm, attributed to amide bond Alg-DA-x -1 And respectively belongs to the absorption peaks of an amide II band and an amide III band of Alg-DA-x.
(3) Hydrogen spectrum of nuclear magnetic resonance 1 H NMR analysis
10mg of Alg and Alg-DA-x are weighed and placed in a nuclear magnetic tube respectively, 700. Mu.L of 99.9% deuterated water is added and fully dissolved under the assistance of ultrasound. After complete dissolution, the chemical structure of the samples was checked by means of a DMX500 NMR spectrometer (Bruker, switzerland).
Of Alg and Alg-DA-x 1 H NMR is shown in FIG. 2 (b). The chemical shifts of the proton peaks on the Alg backbone (Lin et al, 2021) are predominantly in the chemical shifts δ 3.6-5.0ppm. Compared with Alg, alg-DA-x adds several new peaks on 1H NMR, wherein a proton peak at a chemical shift delta 2.8ppm is assigned to a proton peak of a methylene group on DA, delta 3.1ppm is assigned to a proton peak of a methylene group on DA close to an amido bond, and delta 6.6-6.9ppm is assigned to a proton peak on a benzene ring of DA. Notably, for the comparison of the four samples of Alg-DA-x 1 H NMR, since a sample having a high pH value is easily oxidized and polymerized under alkaline conditions. Therefore, the proton peak intensity of the sample with higher pH value gradually decreases. This indicates that four pH-adjusted dopamine-functionalized alginic acid derivatives were successfully prepared.
(4) Ultraviolet visible spectrum (UV) analysis
Respectively dissolving a certain amount of Alg and Alg-DA-x in deionized water to prepare a solution, and performing spectrum scanning on the sample solution within a scanning range of 200-400nm by using a Lambda 750s ultraviolet spectrophotometer.
The ultraviolet spectra of Alg and Alg-DA-x are shown in FIG. 3 (a). The ultraviolet spectrum of Alg solution has no Alg absorption peak in the wavelength range of 230-400nm, while Alg-DA-x solution has a distinct absorption peak at 280nm (Lee et al, 2021). This is due to the fact that DA is grafted to Alg, the catechol group gives rise to UV absorption at 280nm and the greater this absorption peak intensity is for Alg-DA-x samples with higher pH. This is probably because as the pH value increases, the absorption peak is enhanced because the amino group which is a co-chromophore due to disproportionation is easily attached to the phenyl group of DA.
(5) Thermogravimetric (TGA) analysis
Weighing about 8mg of Alg and Alg-DA-x samples, and determining the thermal stability of the samples by a TA Q600 thermal analyzer under nitrogen purging, wherein the flow rate of the nitrogen purging is 20mL/min, the test temperature range is 30-800 ℃, and the heating rate is 10 ℃/min.
Thermogravimetric analysis (TGA) of Alg and Alg-DA-x is shown in FIG. 3 (b). In the TGA study, the weight residuals at 800 ℃ of Alg, alg-DA-5.3, alg-DA-6.8, alg-DA-8.3 and Alg-DA-9.8 were 20.96%, 29.89%, 30.39%, 32.28% and 37.58%, respectively. Alg and Alg-DA-x have two processes in the thermal degradation stage, the first stage at 40-160 ℃, mainly due to the loss of physically adsorbed water in this stage; the second stage is from 220 to 250 ℃, the thermal degradation of this stage being mainly due to dehydroxylation of the structural water and decomposition of organic groups at high temperature (Qin et al, 2014). Alg showed significant thermal degradation as the temperature rose to 550 ℃, while Alg-DA-x showed insignificant thermal degradation, and the higher the weight retention of Alg-DA-x with the higher pH. These results further demonstrate that four pH adjusted dopamine functionalized alginic acid derivatives were successfully prepared and that the higher the pH the better the thermal stability of the Alg-DA-x sample.
(6) Gel Permeation Chromatography (GPC) analysis
Molecular weights of Alg and Alg-DA-x were determined using a Waters2695 high performance liquid chromatography system. The sample concentration was 2g/L, the mobile phase was 0.05wt% sodium azide solution, and the flow rate was 0.6mL/min. The chromatographic columns used were Ultrahydrogel 500 and Ultrahydrogel 120 in series. The temperature of the chromatographic column is kept at 45 ℃, the detector is a differential refractive index detector, and the test method is gel permeation chromatography.
The molecular weights of Alg and Alg-DA-x were determined by gel permeation chromatography, and the results are shown in Table 1. The number average molecular weight M of Alg-DA-x can be seen from the table n And a weight average molecular weight M w All are larger than Alg, and the higher the pH value of the Alg-DA-x sample is, the M thereof is w And M n The higher. This is mainly due to the oxidative polymerization of DA into dimers or multimers that promote the linkage between the Alg-DA-x chains.
TABLE 1 molecular weights of Alg and Alg-DA-x
2. Properties of Alg-DA-x
(1) Study of self-Assembly behavior of aqueous solutions
1g/L of Alg-DA-5.3, alg-DA-6.8, alg-DA-8.3 and Alg-DA-9.8 were prepared with deionized water, respectively. The aqueous solution was added dropwise to a copper mesh. After drying by an infrared lamp, the micelles were stained with 2% phosphorus tungstate, and the micelle morphology was observed by a Talos F200X transmission electron microscope (Thermo scientific, america) at an accelerating voltage of 200 kV.
The sample is dissolved and prepared into a solution with a certain concentration, and the particle size and the Zeta potential of the solution are measured by a dynamic light scattering instrument, wherein the instrument adopts a He-Ne light source, the scattering angle is 90 degrees, and the testing temperature is 25 ℃. All sample tests were performed in triplicate and averaged.
The Zeta potential and the particle size of the Alg-DA-x self-assembled micelle are shown in FIG. 4 (a). For the particle size of 4 samples of Alg-DA-x, the particle size of the Alg-DA-5.3 self-assembled micelle was the smallest and the size was 162.73. + -. 13.84nm, and the particle size of the Alg-DA-9.8 self-assembled micelle was the largest and the size was 711.33. + -. 23.46nm. For the Zeta potential of 4 samples of Alg-DA-x, the potential of the Alg-DA-5.3 micelle was the largest and the size was-67.57. + -. 2.59mV, and the potential of the Alg-DA-9.8 micelle was the smallest and the size was-27.93. + -. 2.08mV. The reason is mainly that due to the increase of the pH value of the Alg-DA sample, a large amount of DA undergoes disproportionation reaction and is oxidized and polymerized into a dimer or polymer, and as the polymerization reaction progresses, the electrostatic repulsion force is reduced, self-assembled particles tend to aggregate, and the particle size is increased.
The appearance of the self-assembled particles of the sample was observed by a Transmission Electron Microscope (TEM) (FIG. 4 (b)), alg-DA-5.3 formed a random polymer network aggregate in an aqueous solution, alg-DA-6.8 formed a structure in which a relatively aggregated polymer network coexists with the self-assembled particles, alg-DA-8.3 formed self-assembled particles without a polymer network, and Alg-DA-9.8 formed relatively aggregated self-assembled particles. This is probably because DA undergoes disproportionation reaction and is oxidatively polymerized into a dimer or a multimer with an increase in x in Alg-DA-x, the Zeta potential decreases, the electrostatic repulsive force between polymers decreases, and non-covalent binding interactions such as hydrogen bonds between molecules cause molecular chains to be gathered in a state of being squashed.
(2) Ultraviolet screening determination of Alg-DA-x aqueous solution
1g/L of Alg-DA-5.3, alg-DA-6.8, alg-DA-8.3 and Alg-DA-9.8 were prepared with deionized water, respectively. Adding a proper amount of methylene blue dye into the mixture for dyeing, continuously irradiating for 48 hours by an ultraviolet lamp, and respectively recording the fading states of the methylene blue dye before and after irradiation.
It can be seen from FIG. 5 (a) that the color of the dye added with Alg-DA-9.8 is not changed much before and after the UV irradiation, while the color of the dye added with Alg-DA-5.3 is changed obviously before and after the UV irradiation. However, it is not sufficient to evaluate the ultraviolet shielding property of Alg-DA-x by the change of color, and thus a graph of the content change of methylene blue dye before and after ultraviolet irradiation was measured by an ultraviolet spectrophotometer (FIG. 5 (b)). The larger x, the greater the residual content of methylene blue dye after 2 days of uv irradiation. Wherein the content of the methylene blue dye added with Alg-DA-5.3 is 70.2 percent at the minimum, and the content of the methylene blue dye added with Alg-DA-9.8 is 95.8 percent at the maximum. This indicates that Alg-DA-9.8 has excellent UV shielding properties compared to the other samples.
(3) Surface tension (SFT) and Dynamic Contact Angle (DCA) measurements of Alg-DA-x aqueous solutions
20mL of Alg-DA-x solution with a concentration of 1g/L was prepared. The surface tension of the four solutions at the same concentration was measured by platinum plate method using KRUSS full automatic surface tensiometer, and the measurement was repeated 3 times for each solution and averaged.
The dynamic contact angles of the different solutions were measured by the sessile drop method using an expeience a-300 optical contact angle/surface tension measuring instrument. In the test, banana leaves cultivated outdoors are selected as test objects, and deionized water is used for cleaning three times to thoroughly remove dust on the surfaces of the banana leaves. The blade is then cut into small pieces and glued to a slide. The syringe pump picks up the solution and drips onto the blade surface and an image of the liquid droplet is recorded by a high resolution camera. And acquiring and analyzing image data within 0-300s to obtain the dynamic contact angle and the wetting diameter of the liquid drop.
In order to evaluate the deposition performance of Alg-DA-x on the surface of the crop leaves, an expeience A-300 optical contact angle/surface tension meter is adopted to record the deposition process of the solution on the surface of the banana leaves within 300s (FIG. 6 (a)). As x increases, the better the wettability of Alg-DA-x on the blade surface. Generally, the lower the surface tension of the solution, the better the wetting of the solution, and FIG. 6 (b) shows that the lower the surface tension of Alg-DA-x as x increases, a result that is substantially consistent with the deposition of the solution in FIG. 6 (a). In order to accurately compare the deposition properties of Alg-DA-x, the wetting diameter (FIG. 6 (c)) and the dynamic contact angle (FIG. 6 (d)) of the solution on the blade surface were plotted. The wetting diameters at 300s of the blade surface for Alg-DA-5.3, alg-DA-6.8, alg-DA-8.3 and Alg-DA-9.8 were 0.557mm,0.640mm,0.723mm and 0.806mm, respectively, and the dynamic contact angles were 85.55 °,76.25 °,74.62 ° and 68.9 °, respectively. The above results show that Alg-DA-9.8 has the smallest dynamic contact angle and the largest wetting diameter on the blade. This indicates that Alg-DA-9.8 has excellent deposition properties on the blade surface.
(4) Measurement of adhesion of Alg-DA-x aqueous solution
Dripping 2 mu L of rhodamine B dye with the concentration of 2mM into 8mL of Alg-DA-x solution with the concentration of 1g/L for dyeing, dripping a small amount of dyeing liquid on the banana leaves, and taking a fluorescent microscope picture of the liquid drops on the banana leaves before washing by using an ECLIPSE Ni-E upright electric microscope after the banana leaves are dried in the air. And (3) soaking the banana leaves in deionized water for 15min, taking out and drying, and taking a fluorescence microscope picture of liquid drops on the washed banana leaves by using the upright electric microscope again. The fluorescence coverage area and fluorescence intensity before and after washing with the liquid drops on the banana leaves were analyzed by Image J software.
In order to observe the retention performance of Alg-DA-x on the surfaces of banana leaves, fluorescent imaging is carried out on samples of the leaves before and after washing. The fluorescence photographs of the Alg-DA-x solution before and after soaking on the surface of banana leaf are shown in FIG. 7 (a), from which it can be observed that the highest fluorescence intensity of Alg-DA-9.8 after washing is observed, while the lowest fluorescence intensity of Alg-DA-5.3 after washing is observed. Another point to note is that the spread of the droplets over the vanes is irregularly rounded, primarily due to the wetting anisotropy of the droplets on the vanes. However, it is not accurate to judge the retention of the liquid droplets on the blade from the picture alone. Therefore, we further quantitatively analyzed the retention performance of the droplets by Image J software (fig. 7 (b)). The research result shows that the fluorescence loss rate of Alg-DA-5.3 is 90.4%, and the fluorescence loss rate of Alg-DA-9.8 is 30.8%. These results clearly show that Alg-DA-9.8 has good adhesion and retention properties on crop leaves compared to the other sample solutions.
3. Preparation of emulsions and Properties thereof
(1) Preparation of the emulsion
Deionized water is used for preparing 1g/L of Alg-DA-x solution as a water phase, liquid paraffin is selected as an oil phase, and the prepared Alg-DA-x is respectively added into the liquid paraffin (the oil-water ratio is 1. Preparation of the emulsion obtained by shearing at room temperature for 6min at a rotational speed of 22000r/min with a FA25 high shear emulsifier (FLUKOF, germany) and named EAD-x (EAD-5.3, EAD-6.8, EAD-8.3, alg-DA-9.8) from an emulsion of Alg-DA-x (Alg-DA-5.3, alg-DA-6.8, EAD-8.3 and EAD-9.8). EAD-x used in subsequent experiments was prepared by this method.
(2) Emulsion stability evaluation
The morphology of the emulsion was observed using an Eclipse E200 optical microscope from nikon, japan, and the size and distribution of the emulsion droplets were counted and calculated by Nano measurer software. An emulsion was prepared starting from styrene and 2.0mol% of AIBN. Polymerizing and curing the product emulsion at 65 ℃ for 24 hours, collecting cured emulsion particles, and cleaning the particles by deionized water under vacuum filtration. And finally drying for 24h at 40 ℃ to obtain the solidified emulsion. The solidified emulsion is placed on an object stage and sputtered with gold spraying, and the appearance of the solidified emulsion is observed through a Phenom ProX scanning electron microscope. The stability of the emulsions was evaluated by Turbiscan Stability Index (TSI) and static stability. TSI was obtained from a Turbiscan Lab Expert stability Analyzer. The static stability of the emulsions was evaluated by observing and comparing the changes in the height of the emulsions after 15 minutes, 7 days and 30 days of standing of the emulsions.
Generally, the more uniform the distribution of emulsion droplets, the smaller the droplet size, and the better the stability. In FIG. 8 (a), the emulsion droplets of EAD-9.8 were most uniformly distributed and the droplet size was the smallest in all emulsion samples. However, it is somewhat deficient from the visual observation of the emulsion photograph, and for better measuring and comparing the droplet size distribution of the emulsion sample, the droplets of the emulsion microscopic photograph were counted and calculated by the Nano measurer software, and the result thereof is shown in fig. 8 (b). The size distribution ranges of the emulsion droplets of EAD-5.3, EAD-6.8, EAD-8.3 and EAD-9.8 are 49.0-267.0um,19.0-142.0um,18.0-125.0um and 18.0-78.0um, respectively. It is noted that as x increases, the average size of the emulsion droplets becomes progressively smaller and more uniformly distributed, with EAD-9.8 having the smallest size and most uniformly distributed, primarily in the range of 18.0-33.0um. These results indicate that EAD-9.8 has good stability.
To further compare the emulsion stability of EAD-x, the change profile of emulsion TSI values and the histogram of the change in emulsion height over 30 days were determined. Generally, the smaller the TSI value of an emulsion, the better its stability (Wang et al, 2018 a). FIG. 9 (c) shows the TSI values of EAD-x over time, with the TSI values of the samples decreasing with increasing x. FIG. 9 (d) is a histogram of emulsion height after 15 minutes, 7 days and 30 days of standing for EAD-x. The height of the emulsions after 7 days of standing of EAD-5.3 and EAD-6.8 was significantly reduced due to the poor stability of EAD-5.3 and EAD-6.8 and oil-water separation in the emulsions during standing. Whereas EAD-8.3 and EAD-9.8 showed little change in the height of the emulsion after 7 days and 30 days of standing. And EAD-9.8 still maintains a high emulsion height after standing for 30 days. These results further demonstrate the good stability of EAD-9.8.
In order to study the adsorption of Alg-DA-x with different self-assembly structures on an oil-water interface and an emulsion stabilization mechanism, the adsorption of Alg-DA-x on the surface of a styrene oil drop is studied by an emulsion curing method (Liu et al, 2010). In order to prepare Alg-DA-x stable styrene emulsion, styrene (containing 2% by mol of azobisisobutyronitrile) was used as an oil phase instead of liquid paraffin, and the morphology of the surface of the emulsion microspheres was observed by SEM after the emulsion was solidified (fig. 10 (a)). Experiments show that the surface of the Alg-DA-5.3 stable styrene microspheres is smoother, while the surface of the Alg-DA-6.8, alg-DA-8.3 and Alg-DA-9.8 stable styrene microspheres is rougher, and the rough surfaces are formed by adhering spherical colloid particles on styrene. To further illustrate the adsorption mechanism of the self-assembled structure of Alg-DA-x at the oil-water interface, we plot the mechanism diagram of the stable emulsion of Alg-DA-x (FIG. 10 (b)). The two samples tend to disperse in the continuous phase due to electrostatic repulsion because of the fact that Alg-DA-5.3 is adsorbed on the surface of oil drops in the form of polymer chains on the surface of microspheres and Alg-DA-6.8 is adsorbed on the surface of oil drops in the form of polymer chains with colloid particles on the surface of microspheres. The Alg-DA-8.3 and the Alg-DA-9.8 are adsorbed on the surfaces of oil drops in the form of colloid particles on the surfaces of the microspheres, and it is worth noting that the Alg-DA-9.8 has the highest adsorption degree on the surfaces of the oil drops and forms a relatively dense particle network, and the network structure formed by the combination of the particles improves the gel structure of the emulsion and the stability of the system.
(3) UV screening and rheology testing of emulsions
The uv screening of the emulsions was evaluated by observing and comparing the changes in the height of the emulsions after 0.5, 10 and 48 hours of uv irradiation. Rheology of the emulsion was measured by Discovery HR-2 rotational rheometer (TA, USA). First, an emulsion was subjected to oscillatory strain scanning at a frequency of 1Hz in the strain range of 0.1-1000%Testing, and determining a Linear Viscoelastic Region (LVR) thereof; secondly, in the angular frequency range of 0.1-1000rad/s, the emulsion with 1 percent of oscillation strain is subjected to an angular frequency scanning experiment to evaluate the viscoelasticity of the emulsion; finally, measuring the emulsion for 0.01-100s -1 Apparent viscosity at shear rate the shear viscosity of the emulsion was evaluated. All measurements were performed at 25 ℃.
From FIG. 11 (a) it can be seen that the emulsion broke after 10 hours of UV irradiation with the addition of EAD-5.3 and EAD-6.8. The EAD-8.3 also breaks emulsion after 48 hours of ultraviolet irradiation, while the EAD-9.8 still keeps a stable state after 48 hours of ultraviolet irradiation. However, it is not sufficient to evaluate the UV-shielding performance of Alg-DA-x by the appearance of the emulsion, and in order to further evaluate the UV-shielding performance of EAD-x, the emulsion heights of the sample emulsions after 10 hours and 48 hours of UV irradiation were compared (FIG. 11 (b)). The heights of the emulsion emulsions of EAD-5.3 and EAD-6.8 after being irradiated by an ultraviolet lamp for 10 hours are both 0, which indicates that the ultraviolet shielding performance of EAD-5.3 and EAD-6.8 is poor, so that the emulsion is broken under the irradiation of the ultraviolet light. The emulsion height was 0 after 48 hours of UV irradiation with EAD-8.3, while the emulsion height remained 9.577cm after 48 hours of UV irradiation with EAD-9.8. These results indicate that EAD-9.8 has good UV shielding properties.
FIG. 11 (c) shows that the apparent viscosity of EAD-x gradually decreases with increasing shear rate, showing the shear-thinning behavior of non-Newtonian fluids (Lu et al, 2019). And at any shear rate, the apparent viscosity of EAD-x increases with increasing x. This indicates that EAD-9.8 has a higher emulsion viscosity than the other EAD-x. FIG. 11 (d) shows the strain sweep curve for EAD-x. The strain of the linear viscoelastic region is selected to be 1% when the dynamic oscillation frequency scanning is carried out through a strain scanning test. As can be seen from FIG. 11 (e), the storage modulus (denoted by G') of EAD-x is greater than the loss modulus (denoted by G ") over the sweep range of the dynamic oscillation frequency, indicating that the emulsion has good viscoelasticity. And G' of EAD-9.8 are both obviously larger than those of other sample emulsions, which further indicates that EAD-9.8 has a tightly connected colloidal particle network structure which tightly wraps emulsion droplets, thereby effectively limiting the migration and collision of the droplets.
4. Preparation and Properties of drug-loaded emulsions
Avermectin (AVM) is used as an efficient and broad-spectrum insecticide and acaricide, the chemical structure of the avermectin is composed of a group of sixteen-membered macrolide compounds, and the avermectin has stomach toxicity and contact poisoning effects on mites or insects. The product is white or yellow crystal, has melting point of 150-155 deg.C, solubility of 7.8mg/L in water at 21 deg.C, and high solubility in organic solvent. By spraying the abamectin on the surface of the leaves, the nerve conduction of the arthropod can be effectively inhibited, and meanwhile, the abamectin has a strong penetrating effect on the leaves, and can kill pests below the epidermis or paralyze and kill target insects. However, the strong hydrophobicity of AVM results in poor diffusion during application. In addition, research shows that the molecular structure of the AVM is sensitive to ultraviolet light and is easily degraded under the irradiation of ultraviolet light, which greatly limits the application of the AVM. Therefore, the development of a drug carrier which has high drug encapsulation efficiency, has a photoprotective effect on the AVM, and can effectively deposit and retain the AVM on the surface of the crop leaves is an effective strategy for improving the AVM utilization rate.
(1) Preparation of drug-loaded emulsions
25mg of Abamectin (AVM) was dissolved in 10mL of liquid paraffin with stirring, and the liquid paraffin was mixed with 1mg/mL of Alg-DA-x (oil-water volume ratio of 1. The avermectin loaded emulsion was sheared through a FA25 high shear dispersion homogenizer (FLUKO, germany) at a speed of 22,000rpm on the oil-water mixture for 6 minutes. The AVM supported emulsion stabilized by Alg-DA-x is named AVM @ EAD-x (AVM @ EAD-5.3, AVM @ EAD-6.8, AVM @ EAD-8.3, AVM @ EAD-9.8). AVM @ EAD-x used in subsequent experiments was prepared by this method.
The content of AVM in AVM @ EAD-x was determined by measuring its absorbance. The supernatant was centrifuged at 10,000rpm for 10 minutes at AVM @ EAD-x and the absorbance measured by high performance liquid chromatography (Waters 2695, USA) at 245 nm. The Encapsulation Efficiency (EE) of AVM @ EAD-x is calculated by the following equation (1):
to investigate the controlled release properties of AVM loaded emulsions. Prepared avm @ ead-x was loaded into dialysis bags (molecular weight cut-off Mw =1 kDa), which were soaked in 100mL methanol/water solution (3,7,v/v). The AVM cumulative release amount is calculated by the following calculation formula (2):
as shown in FIG. 12 (a), the encapsulation efficiencies of AVM @ EAD-5.3, AVM @ EAD-6.8, AVM @ EAD-8.3 and AVM @ EAD-9.8 for AVM were 40.25%,46.11%,68.58% and 85.27%, respectively. These results indicate that EAD-9.8 has excellent encapsulation capabilities for AVM. This is probably because EAD-9.8 has good emulsion stability and a tightly connected colloidal particle network structure that tightly encapsulates emulsion droplets, effectively limiting the release of AVM.
FIG. 12 (b) is an AVM cumulative release profile of AVM @ EAD-x over time. In contrast to the AVM cumulative release of AVM @ EAD-x, the cumulative release of AVM @ EAD-x gradually decreases as x increases. In addition, AVM @ EAD-5.3 has burst release during the release process, and the cumulative release reaches 84.52% in the release period, while AVM @ EAD-9.8 has the slowest release process and only has the cumulative release of 46.58% in the release period. This is mainly due to the low encapsulation efficiency of AVM @ EAD-5.3, the dissolution of unencapsulated AVM into aqueous methanol after soaking in aqueous methanol, and the release of AVM into aqueous methanol due to emulsion breaking during the release of AVM due to poor emulsion stability. And as x is increased, the encapsulation efficiency of AVM @ EAD-x is increased, the stability of the emulsion is increased, the cumulative release is smaller and the release speed is slower.
(2) Light degradation resistance test of drug-loaded emulsion
To study the photodegradation behavior of AVM under UV light, the residual AVM content of AVM @ EAD-x under different irradiation times was determined by high performance liquid chromatography (Waters 2695, USA) by dropping an appropriate amount of AVM @ EAD-x into a 9.0 cm diameter petri dish, then placing the petri dish under UV light of power 30W and irradiation wavelength 310nm, setting the sampling time intervals (1, 3, 5, 8, 12, 24 and 48 h), and plotting the drug degradation curves.
As shown in FIG. 13, the AVM @ EAD-5.3 retention rate after 48 hours of UV irradiation was less than 20%, while AVM @ EAD-9.8 retention rate after 48 hours of UV irradiation was 73.55% and all were greater than the other drug loaded emulsion samples. The reason is that the EAD-5.3 is used as a drug carrier, the ultraviolet shielding performance and the emulsion stability are poor, emulsion breaking and oil-water separation occur in the emulsion under the irradiation of ultraviolet light, and the AVM in the oil phase is degraded under the exposure of the ultraviolet light. And as x is increased, the ultraviolet shielding performance and stability of the emulsion are improved, so that the residual rate of AVM under ultraviolet irradiation is increased. These results indicate that EAD-9.8 as a pesticide carrier is effective in protecting AVM from sunlight.
(3) Measurement of Dynamic Contact Angle (DCA) and wetting diameter of drug-loaded emulsions
The dynamic contact angle of AVM @ EAD-x was determined by the sessile drop method using an expeience A-300 optical contact angle/surface tension meter. In the test, outdoor cultivated banana leaves are selected as test objects, and deionized water is used for cleaning three times to thoroughly remove dust on the surfaces of the leaves. The blade is then cut into small pieces and glued to a slide. AVM @ EAD-x was picked up by the injection pump and dripped on the blade surface. Images of the emulsion droplets were recorded by a high resolution camera. And acquiring and analyzing image data of the emulsion liquid drop within 0-300s to obtain the dynamic contact angle and the wetting diameter of the liquid drop. To ensure the reliability of the data, each set of experiments was measured in triplicate and averaged.
The results are shown in FIG. 14. The deposition of the drug-loaded emulsion on the banana leaf surface within 300s was recorded using an expeience a-300 optical contact angle/surface tension meter (fig. 14 (a)). The deposition process of AVM @ EAD-9.8 on the blade is evident from the figure. To more accurately evaluate the deposition performance of AVM @ EAD-x, the dynamic contact angle (FIG. 14 (b)) and wetting radius (FIG. 14 (c)) were plotted. The wetting diameters of AVM @ EAD-5.3, AVM @ EAD-6.8, AVM @ EAD-8.3 and AVM @ EAD-9.8 at the blade surface 300s were 0.621mm,0.641mm,0.734mm and 0.790mm, respectively, and the dynamic contact angles were 82.36 °,77.46 °,56.52 ° and 45.21 °, respectively. The above results show that AVM @ EAD-9.8 has the smallest dynamic contact angle and the largest wetting diameter on the blade, which indicates that AVM @ EAD-9.8 has excellent deposition performance on the blade surface.
The embodiments of the present invention have been described in detail, but the embodiments are only examples, and the present invention is not limited to the embodiments described above. Any equivalent modifications and substitutions for the present invention are within the scope of the present invention for those skilled in the art. Accordingly, equivalent changes and modifications made without departing from the spirit and scope of the present invention should be covered by the present invention.
Claims (10)
1. A dopamine functionalized alginic acid derivative is characterized in that the dopamine functionalized alginic acid derivative is a mixture of compounds shown in a structural formula (1) and a structural formula (2),
2. the dopamine-functionalized alginic acid derivative according to claim 1, which is obtained by oxidative polymerization of dopamine-functionalized sodium alginate represented by structural formula (3):
preferably, the oxidative polymerization reaction occurs at an ambient pH of 5.3 or more, preferably at a pH of 6.8 or more, more preferably at a pH of 7 or more, even more preferably at a pH of 8.3 or more, and even more preferably at a pH of 9.8 or more.
3. The dopamine-functionalized alginic acid derivative according to any of claims 1-2, characterized in that it has a weight-average molecular weight of more than or equal to 60000, preferably 600000-1200000.
4. A process for the preparation of a dopamine-functionalized alginic acid derivative according to any one of claims 1 to 3, comprising the following steps: (1) Fully activating carboxyl of sodium alginate by EDC & HCl and NHS, adding dopamine hydrochloride, and fully reacting to obtain dopamine-functionalized sodium alginate; (2) The dopamine functionalized alginic acid derivative is obtained by oxidative polymerization of the obtained dopamine functionalized sodium alginate, preferably, the pH of the environment where oxidative polymerization reaction occurs is more than or equal to 5.3, preferably, the pH is more than or equal to 6.8, more preferably, the pH is more than or equal to 7, further preferably, the pH is more than or equal to 8.3, and even more preferably, the pH is more than or equal to 9.8.
5. An emulsion comprising an oil phase and an aqueous phase, wherein the dopamine-functionalized alginic acid derivative according to any one of claims 1 to 3 or the dopamine-functionalized alginic acid derivative prepared by the preparation method according to claim 4 is used as a stabilizer.
6. The emulsion of claim 5, wherein the volume ratio of the oil phase to the aqueous phase of the emulsion is 1: 0.1-10, and the concentration of the dopamine-functionalized alginic acid derivative in the aqueous phase is 0.1-10g/L.
7. A drug-loaded emulsion, which is characterized in that the drug-loaded emulsion comprises an oil phase and an aqueous phase, the dopamine-functionalized alginic acid derivative as claimed in any one of claims 1 to 3 or the dopamine-functionalized alginic acid derivative as prepared by the preparation method as claimed in claim 4 is used as a stabilizer, and a drug is dissolved in the oil phase or the aqueous phase.
8. The drug-loaded emulsion of claim 7, wherein the volume ratio of the oil phase to the water phase of the drug-loaded emulsion is 1: 0.1-10, the concentration of the dopamine-functionalized alginic acid derivative in the water phase is 0.1-10g/L, and preferably, the oil phase is liquid paraffin containing abamectin.
9. Use of a dopamine-functionalized alginic acid derivative according to any one of claims 1 to 3 or an emulsion according to claim 5 or 6 or a drug-loaded emulsion according to claim 7 or 8 in the fields of biomedicine, cosmetics, food, petroleum and wastewater treatment.
10. Use of a dopamine-functionalized alginic acid derivative according to any one of claims 1 to 3 or an emulsion according to claim 5 or 6 or a drug-loaded emulsion according to claim 7 or 8 for the preparation of a slow release formulation of a drug.
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| CN102964610A (en) * | 2012-11-16 | 2013-03-13 | 天津大学 | Preparation method of polydopamine modified alginic acid microspheres |
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| CN113509402A (en) * | 2021-07-09 | 2021-10-19 | 江南大学 | Preparation method of sodium alginate-dopamine copolymer/ferrous ion antibacterial agent on tooth surface |
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| CN102964610A (en) * | 2012-11-16 | 2013-03-13 | 天津大学 | Preparation method of polydopamine modified alginic acid microspheres |
| CN106267337A (en) * | 2016-09-07 | 2017-01-04 | 江南大学 | A kind of preparation method of DOPA amido function-graded material |
| CN107149702A (en) * | 2017-05-12 | 2017-09-12 | 江南大学 | A kind of preparation of poly-dopamine modified lithium porous support |
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