Water-in-water-in-water emulsion for drug delivery and preparation method and application thereof

Abstract

The invention relates to the technical field of drug delivery, and mainly relates to a water-in-water-in-water emulsion for drug delivery and a preparation method and application thereof. The preparation method comprises the following steps: preparing an anionic polysaccharide aqueous solution, and dissolving a medicine in the anionic polysaccharide aqueous solution to obtain a mixed solution; preparing a cationic polysaccharide aqueous solution or a protein aqueous solution; and adding the mixed solution into a cationic polysaccharide aqueous solution or a protein aqueous solution, mixing, and emulsifying to obtain the water-in-water-in-water emulsion for drug delivery. The water-in-water-in-water emulsion with high stability and excellent biocompatibility is successfully prepared through the synergistic effect of the cationic polysaccharide or the protein and the anionic polysaccharide without any emulsifier, and the unique particle structure of the emulsion is combined with a charge conversion mechanism to regulate and control drugs, realize slow release and prolong the drug effect time.

Description

Technical Field

[0001] The present application relates to the technical field of drug delivery, and mainly to a water-in-water-in-water emulsion for drug delivery and a preparation method and application thereof. Background Art

[0002] Emulsion drug delivery is a delivery system that dissolves or disperses the drug in a mixture of oil phase and water phase through an emulsifier. It is usually used to improve the bioavailability of the drug, improve the solubility of the drug or achieve a more stable drug release. However, traditional emulsions have some disadvantages, and the following problems need to be solved urgently: (1) Low drug delivery efficiency: Traditional emulsions often have problems such as insufficient adhesion to the gastrointestinal tract and low drug bioavailability. (2) Instability: ① The oil and water phases of the emulsion may stratify over time, resulting in the separation of the oil phase and the water phase, thereby affecting the uniformity and dosage accuracy of the drug. ② The tiny particles in the emulsion may aggregate or coagulate, causing the emulsion to become turbid or lose its original drug delivery effect. (3) Emulsifier selection problem: ① Some emulsifiers may not be well compatible with the human body and may cause local irritation or allergic reactions. ② Excessive use of emulsifiers may be harmful to the human body or cause allergic reactions. ③ Some highly efficient emulsifiers are expensive, which increases production costs. Therefore, it is necessary to provide an emulsion system that can be stable and well adhered to achieve efficient drug targeted delivery. Therefore, the prior art still needs to be improved and developed. Summary of the invention

[0003] In view of the above-mentioned deficiencies in the prior art, the purpose of the present application is to provide a water-in-water-in-water emulsion for drug delivery and a preparation method and application thereof, aiming to solve the problems of low drug delivery efficiency, low stability and easy irritation of existing traditional emulsions.

[0004] The technical solution of this application is as follows: In a first aspect, the present application provides a method for preparing a water-in-water-in-water emulsion for drug delivery, comprising the following steps: preparing an anionic polysaccharide aqueous solution, and dissolving the drug in the anionic polysaccharide aqueous solution to obtain a mixed solution; preparing a cationic polysaccharide aqueous solution or a protein aqueous solution; The mixed solution is added into the cationic polysaccharide aqueous solution or the protein aqueous solution, mixed and then emulsified to obtain the water-in-water-in-water emulsion for drug delivery.

[0005] The preparation method of the present application can produce a stable water-in-water-in-water emulsion. It is speculated that when the cationic aqueous solution or the protein aqueous solution is mixed with the anionic aqueous solution, the solution concentration is high, and the two macromolecules interact with each other to form a lot of nano-scale coagulation particles as the inner water phase, so that the concentration of macromolecules around the nano-scale coagulation particles is reduced. The outermost layer of the nano-scale coagulation particles is coated with cationic polysaccharide macromolecules or protein macromolecules, and the positively charged macromolecules attract the negatively charged anionic polysaccharide macromolecules to aggregate, gradually forming micron-scale coagulation particles around the nano-scale coagulation particles as the outer water phase. A polysaccharide equilibrium solution is finally formed around the micron-scale coagulation particles as the outermost water phase. In this process, partially dissolved drugs are encapsulated in the coagulation particles to achieve the effects of targeting and sustained release. Inside the agglomerate particles, the charge distribution of polysaccharide (or protein) macromolecules is uneven, there is electrostatic complexation between anionic macromolecules and cationic macromolecules, and there is electrostatic repulsion in the non-complexed area. Therefore, a certain amount of drug solution can be enclosed in the agglomerate particles, while the outside of the micron-sized agglomerate particles is coated by molecules with the same charge. Charges of the same kind repel each other, which is conducive to the stability of the emulsion.

[0006] Further, the concentration of the anionic polysaccharide in the mixed solution is 0.25%-2.0%; The concentration of the cationic polysaccharide aqueous solution or protein aqueous solution is 0.25%-2.0%.

[0007] Further, the concentration of the anionic polysaccharide in the mixed solution is the same as the concentration of the cationic polysaccharide aqueous solution, and the volume ratio of the mixed solution to the cationic polysaccharide aqueous solution is 1:1.2; Or the concentration of the anionic polysaccharide in the mixed solution is the same as the concentration of the protein aqueous solution, and the volume ratio of the mixed solution to the protein aqueous solution is 1:1.2.

[0008] Furthermore, the emulsification method is one of high shear emulsification, ultrasonic treatment and high pressure homogenization.

[0009] Furthermore, the emulsification method is high-pressure homogenization, the rotation speed is 10000-20000 rpm, and the processing time is 30s-3min.

[0010] Furthermore, the concentration of the drug in the mixed solution is 0.1-2 mg / ml, and the drug is one of amoxicillin, levofloxacin, and clarithromycin.

[0011] Furthermore, the anionic polysaccharide is one or more of sodium hyaluronate, sodium alginate, sodium carboxymethyl cellulose, xanthan gum and carrageenan.

[0012] Furthermore, the cationic polysaccharide is one or more of chitosan, polyethyleneimine, and poly(dimethyldiallylammonium chloride); The protein is one of gelatin, whey protein and soy protein isolate.

[0013] In a second aspect, the present application provides a water-in-water-in-water emulsion for drug delivery, wherein the emulsion is prepared by the method for preparing the water-in-water-in-water emulsion for drug delivery as described in the first aspect.

[0014] In a third aspect, the present application provides a use of the water-in-water-in-water emulsion for drug delivery as described in the second aspect, wherein the water-in-water-in-water emulsion for drug delivery is used for drug delivery.

[0015] Beneficial effects: This application successfully prepares a water-in-water-in-water emulsion with high stability and excellent biocompatibility through the synergistic effect of cationic polysaccharides (or proteins) and anionic polysaccharides without using any emulsifiers. The unique particle structure of the emulsion combined with the charge conversion mechanism can regulate the drug, achieve sustained release, and prolong the efficacy time. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 Schematic diagram of the structure of the water-in-water-in-water emulsion for drug delivery in the present application.

[0017] Figure 2 This is a physical picture of the water-in-water-in-water emulsion for drug delivery prepared in Example 1 of the present application.

[0018] Figure 3 This is an electron microscope image of the water-in-water-in-water emulsion for drug delivery prepared in Example 1 of the present application at a scale of 5 um.

[0019] Figure 4 This is an electron microscope image of the water-in-water-in-water emulsion for drug delivery prepared in Example 3 of the present application at a scale of 5 um.

[0020] Figure 5 This is an electron microscope image of the water-in-water-in-water emulsion for drug delivery prepared in Example 4 of the present application at a scale of 5 um.

[0021] Figure 6 This is an electron microscope image of the water-in-water-in-water emulsion for drug delivery prepared in Example 5 of the present application at a scale of 5 um.

[0022] Explanation of reference numerals: 1. Nano-scale condensed particles; 2. Micro-scale condensed particles; 3. Polysaccharide equilibrium solution. DETAILED DESCRIPTION

[0023] The present application provides a water-in-water-in-water emulsion for drug delivery and a preparation method and application thereof. To make the purpose, technical solution and effect of the present application clearer and more specific, the present application is further described in detail below. It should be understood that the specific embodiments described herein are only used to explain the present application and are not used to limit the present application.

[0024] The present application provides a method for preparing a water-in-water-in-water (W / W / W) emulsion for drug delivery, specifically comprising the following steps: S1. preparing an anionic polysaccharide aqueous solution, and dissolving the drug in the anionic polysaccharide aqueous solution to obtain a mixed solution; S2. preparing a cationic polysaccharide aqueous solution or a protein aqueous solution; S3. Adding the mixed solution to the cationic polysaccharide aqueous solution or the protein aqueous solution, mixing and emulsifying to obtain a water-in-water-in-water emulsion for drug delivery.

[0025] In step S1, the drug can be dissolved by stirring at a speed of 300-1000 r / min for 0.5-5 hours until it is completely dissolved or mixed evenly. The drug can also be pre-dissolved in water to form a drug solution, and then added to the anionic polysaccharide aqueous solution for mixing evenly, so that the drug can be better dissolved and the mixing effect can be ensured.

[0026] The present application successfully prepares a water-in-water-in-water emulsion with high stability and excellent biocompatibility through the synergistic effect of cationic polysaccharides or proteins and anionic polysaccharides without using any emulsifiers. The unique particle structure of the emulsion combined with the charge conversion mechanism can regulate the drug, achieve sustained release, and prolong the duration of drug efficacy.

[0027] Specifically, a stable water-in-water-in-water emulsion can be prepared by the preparation method of the present application. It is speculated that when the cationic aqueous solution or the protein aqueous solution is mixed with the anionic aqueous solution, the solution concentration is high, and the two macromolecules interact with each other to form a lot of nanoscale coacervate particles as the inner water phase, so that the concentration of macromolecules around the nanoscale coacervate particles is reduced. The outermost layer of the nanoscale coacervate particles is coated with cationic polysaccharide macromolecules or protein macromolecules, and the positively charged macromolecules attract the negatively charged anionic polysaccharide macromolecules to aggregate, gradually forming micron-sized coacervate particles around the nanoscale coacervate particles as the outer water phase. A polysaccharide equilibrium solution is finally formed around the micron-sized coacervate particles as the outermost water phase. In this process, partially dissolved drugs are encapsulated in the coacervate particles to achieve the effects of targeting and sustained release. Inside the agglomerate particles, the charge distribution of polysaccharide (or protein) macromolecules is uneven, there is electrostatic complexation between anionic macromolecules and cationic macromolecules, and there is electrostatic repulsion in the non-complexed area. Therefore, a certain amount of drug solution can be enclosed in the agglomerate particles, while the outside of the micron-sized agglomerate particles is coated by molecules with the same charge. Charges of the same kind repel each other, which is conducive to the stability of the emulsion.

[0028] There is drug solution in both the agglomerate particles and the polysaccharide equilibrium solution, and part of the drug solution encapsulated in the agglomerate particles can achieve the effects of targeting and sustained release through the emulsion particles adhering to the surface of the gastrointestinal mucosa.

[0029] Further, in step S1, the concentration of the drug in the mixed solution is 0.1-2 mg / ml. In the present application, the drug concentration can be adjusted according to the specific drug properties, the stability of the emulsion and the treatment needs. By controlling the concentration of the drug, it is beneficial to ensure the stability of the emulsion and avoid failure of the emulsified structure due to too high concentration.

[0030] Specifically, the drug solution is selected from drugs that do not react with the system or do not affect the structure and stability of the emulsion. Further, in step S1, the drug is one of amoxicillin, levofloxacin, and clarithromycin. Specifically, the drug solution can be prepared into a drug solution of a desired concentration.

[0031] Furthermore, in step S1, the concentration of anionic polysaccharides in the mixed solution is 0.25%-2.0% (w / v). The concentration is a mass volume ratio, and the unit is g / ml. In the present application, too high anion concentration will lead to reduced emulsion stability, and anionic polysaccharides can form agglomerate particles with cationic polysaccharides. Too high or too low anion concentration will affect the charge coordination therein, which may make it difficult to form a water-in-water-in-water emulsion.

[0032] Furthermore, in step S1, the anionic polysaccharide is one or more of sodium hyaluronate, sodium alginate, sodium carboxymethyl cellulose, xanthan gum, carrageenan, etc.

[0033] Furthermore, in step S2, the concentration of the cationic polysaccharide aqueous solution or the protein aqueous solution is 0.25%-2.0% (w / v). The concentration is a mass volume ratio, and the unit is g / ml. In the present application, the cationic polysaccharide needs to form agglomerate particles with the anionic polysaccharide. If the concentration of the cation is too low or too high, it will destroy the charge balance and the water phase distribution balance, and will affect the structure and stability of the emulsion.

[0034] Furthermore, in step S2, the cationic polysaccharide is one or more of chitosan, polyethyleneimine, poly(dimethyldiallylammonium chloride), etc. Furthermore, the cationic polysaccharide is preferably chitosan of natural origin; and the protein is one of gelatin, whey protein, and soy protein isolate.

[0035] Further, in step S3, the concentrations of the anionic polysaccharide aqueous solution and the cationic polysaccharide aqueous solution are the same, and the volume ratio of the mixed solution to the cationic polysaccharide aqueous solution is 1:1.2; or the concentrations of the anionic polysaccharide aqueous solution and the protein aqueous solution are the same, and the volume ratio of the mixed solution to the protein aqueous solution is 1:1.2. In the present application, the amount of cationic polysaccharide has a greater influence on the stability of the emulsion. When the ratio is too low, it is easy to form a water-in-water emulsion, the emulsion is unstable, and it is easy to stratify. It is difficult to form an emulsion after the ratio is lower than a certain range. When the ratio is too high, the charge imbalance affects the formation and distribution of the coagulant, and the water-in-water-in-water structure in the emulsion is reduced. By controlling the proportion of cationic polysaccharides to be appropriately excessive, it is easy to form coagulant particles with anions through electrostatic action, and at the same time, a certain polysaccharide (protein) concentration is maintained in the outermost aqueous phase, as a polysaccharide (protein) solution equilibrium phase stabilizes the emulsion, and at the same time, the same kind of charge provided can perform a certain repulsive effect, prevent the aggregation of emulsion particles, and is conducive to the stability of the emulsion.

[0036] Further, in step S3, the emulsification method is one of high shear emulsification, ultrasonic treatment and high pressure homogenization. Preferably, the emulsification method is high pressure homogenization, which can be specifically processed by a high-speed homogenizer, with a rotation speed of 10000-20000 rpm and a processing time of 30s-3min. In the present application, the ratio of cationic polymer to anionic polymer in solution and the emulsification time have an important influence on the size and stability of the emulsion particles, the rotation speed is too high and the processing time is too long, the emulsion particle size is too small, and it is difficult to form a water-in-water-in-water structure, the rotation speed is too low and the processing time is too short, the emulsion particle size is too large, and the emulsion is easy to stratify and unstable. The present application controls the rotation speed to 10000-20000rpm for 30s-3min, and the drug can be dispersed and wrapped by high shear emulsification, and micron-level agglomerates containing multiple nano-level agglomerates can be formed.

[0037] like Figure 1As shown, the present application also provides a water-in-water-in-water emulsion for drug delivery, wherein the water-in-water-in-water emulsion for drug delivery is prepared by the preparation method of the water-in-water-in-water emulsion for drug delivery as described above. The structure of the prepared water-in-water-in-water emulsion for drug delivery includes: micron-sized agglomerate particles 2 containing a plurality of nano-sized agglomerate particles 1, and the micron-sized agglomerate particles 2 are dispersed in a polysaccharide equilibrium solution 3.

[0038] The preparation method provided in the present application can prepare a water-in-water-in-water emulsion whose basic structure is a micron-sized emulsion particle containing a plurality of nano-sized emulsion particles. Specifically, the nano-sized aggregate particles 1 in the basic structure serve as the inner water phase, the micron-sized aggregate particles 2 serve as the outer water phase, and the polysaccharide equilibrium solution 3 outside the basic structure serves as the outermost water phase, thereby forming a water-in-water-in-water structure.

[0039] The present application utilizes a composite method of cationic polysaccharides (such as chitosan, etc.) and anionic polysaccharides (such as hyaluronic acid, sodium alginate, etc.) to prepare a water-in-water-in-water emulsion that can achieve charge conversion under different pH environments. The emulsion particles can enhance the adhesion to the gastric mucosa in the gastrointestinal tract through a charge conversion mechanism, thereby achieving efficient targeted drug delivery and effective drug sustained release, and can improve the drug delivery efficiency in the gastrointestinal tract.

[0040] The present application also provides an application of the water-in-water-in-water emulsion for drug delivery as described above, and the water-in-water-in-water emulsion for drug delivery is applied to drug delivery. The prepared water-in-water-in-water emulsion can be applied to the delivery of various drugs, and is particularly suitable for the targeted delivery of gastrointestinal drugs. Drugs (such as antibiotics, anticancer drugs, digestive system drugs, etc.) can be loaded through a coacervate phase to obtain longer gastrointestinal retention and slow release. Through the charge conversion mechanism, the drug is released slowly in the stomach, and is rapidly released in stages in the intestine, thereby improving the bioavailability of the drug.

[0041] In the present application, the water-in-water-in-water emulsion provided has charge properties that are adjustable under different pH environments, making it easier to cope with drug delivery in the gastrointestinal tract.

[0042] Specifically, taking chitosan as a cationic polysaccharide as an example, in a gastric acid environment with a pH of 1.2, the amino group (NH2) in the chitosan molecule will be protonated in an acidic environment and carry a positive charge. There is an electrostatic interaction between the positively charged particles and the negatively charged components of the gastric mucosa (such as glycosaminoglycans, gastric proteins, etc.), which enhances the affinity of the particles to the gastric mucosa and the degree of adhesion to the stomach, and increases the retention time of the particles in the stomach. Moreover, the addition of anionic polysaccharides such as hyaluronic acid or sodium alginate can enhance the biocompatibility of the emulsion particles to a certain extent, reduce irritation to the gastrointestinal tract, and thus improve its stability and safety. Enhanced adhesion not only helps to prolong the retention time of the drug in the stomach, but also increases the local concentration of the drug in the gastrointestinal tract, thereby enhancing the therapeutic effect of the drug.

[0043] In the intestinal environment with a pH of 7.4, as the pH increases, the amino groups of chitosan gradually deprotonate and carry a weaker positive charge or a nearly neutral charge. At this time, the affinity of the particles to the intestinal mucosa decreases, reducing the excessive adhesion of the particles in the intestine. At the same time, the interaction between chitosan and anionic polysaccharides weakens, and the micron-sized emulsion particles open, releasing a portion of the drug and the internal nano-sized emulsion particles. As time goes on, the released nano-sized emulsion particles open again to release the drug, achieving sustained release and absorption of the drug.

[0044] The invention is further described below by means of specific examples.

[0045] Embodiment 1: Preparation of anionic aqueous solution: drug solution (such as amoxicillin solution) is added to carrageenan solution to obtain a mixed solution, in which the concentration of drug is 0.5 mg / ml and the concentration of carrageenan is 0.25% (w / v), and the mixed solution is evenly mixed by magnetic stirring at 500 r / min for 1 h.

[0046] Preparation of cationic aqueous solution: The concentration of chitosan solution was 0.25% (w / v), and it was mixed evenly by magnetic stirring at 500 r / min for 1 h.

[0047] Emulsification process: The mixed solution was mixed with the cationic aqueous solution at a ratio of 1:1.2 and processed by a high-speed homogenizer (15000 rpm) for 1 min to form a W / W / W emulsion.

[0048] The actual picture of the water-in-water-in-water emulsion prepared in Example 1 is as follows Figure 2 As shown in FIG. 1 , the present invention can successfully prepare a water-in-water-in-water emulsion with good emulsification performance without using any emulsifier. The electron microscope image of the emulsion is shown in FIG. Figure 3 As shown, it can be found that the basic structure of the prepared emulsion is that the micron-sized emulsion particles contain multiple nano-sized emulsion particles, successfully realizing a water-in-water-in-water structure.

[0049] Embodiment 2: Preparation of anionic aqueous solution: Add drug solution (such as amoxicillin solution) to sodium hyaluronate solution so that the drug concentration in the mixed solution is 1 mg / ml and the sodium hyaluronate concentration is 0.5% (w / v), and mix evenly by magnetic stirring at 500 r / min for 1 h.

[0050] Preparation of cationic aqueous solution: The concentration of chitosan solution was 0.5% (w / v), and it was mixed evenly by magnetic stirring at 500 r / min for 1 h.

[0051] Emulsification process: The mixed solution was mixed with the cationic aqueous solution at a ratio of 1:1.2 and processed by a high-speed homogenizer (10,000 rpm) for 1 min to form a W / W / W emulsion.

[0052] Example 3 Preparation of anionic aqueous solution: Add drug solution (such as amoxicillin solution) to sodium hyaluronate solution so that the drug concentration in the mixed solution is 1 mg / ml and the sodium hyaluronate concentration is 0.5% (w / v), and mix evenly by magnetic stirring at 500 r / min for 1 h.

[0053] Preparation of cationic aqueous solution: The concentration of chitosan solution was 0.5% (w / v), and it was mixed evenly by magnetic stirring at 500 r / min for 1 h.

[0054] Emulsification process: The anion aqueous solution and the cationic aqueous solution were mixed in a ratio of 1:5 and processed by a high-speed homogenizer (10,000 rpm) for 1 min to form a W / W / W emulsion.

[0055] The electron microscope image of the water-in-water-in-water emulsion prepared in Example 3 is as follows: Figure 4 As shown, it can be found that as the proportion of cationic polysaccharides increases, the number of emulsion particles with a water-in-water-in-water structure formed decreases and the particle size distribution range is wide.

[0056] Example 4 Preparation of anionic aqueous solution: Add drug solution (such as amoxicillin solution) to sodium hyaluronate solution so that the drug concentration in the mixed solution is 1 mg / ml and the sodium hyaluronate concentration is 0.5% (w / v), and mix evenly by magnetic stirring at 500 r / min for 1 h.

[0057] Preparation of cationic aqueous solution: The concentration of chitosan solution was 0.5% (w / v), and it was mixed evenly by magnetic stirring at 500 r / min for 1 h.

[0058] Emulsification process: The anion aqueous solution and the cationic aqueous solution were mixed in a ratio of 5:1 and processed by a high-speed homogenizer (10,000 rpm) for 1 minute to form the emulsion of Example 4.

[0059] The electron microscope image of the emulsion prepared in Example 4 is as follows: Figure 5 As shown, it can be found that the proportion of anionic polysaccharides is too large, and there are very few emulsion particles with a water-in-water-in-water structure, and mainly a W / W emulsion is formed.

[0060] Example 5 Preparation of anionic aqueous solution: Add drug solution (such as amoxicillin solution) to sodium hyaluronate solution so that the drug concentration in the mixed solution is 1 mg / ml and the sodium hyaluronate concentration is 0.5% (w / v), and mix evenly by magnetic stirring at 500 r / min for 1 h.

[0061] Preparation of cationic aqueous solution: The concentration of chitosan solution was 0.5% (w / v), and it was mixed evenly by magnetic stirring at 500 r / min for 1 h.

[0062] Emulsification process: The anion aqueous solution and the cationic aqueous solution were mixed in a ratio of 1:1.2 and processed by a high-speed homogenizer (10,000 rpm) for 20 seconds to form a W / W / W emulsion.

[0063] The electron microscope image of the prepared emulsion of Example 5 is as follows Figure 6 As shown, it can be found that when the emulsification time is too short, the emulsion particles with a water-in-water-in-water structure formed will be larger in size, easy to stratify, and have poor stability.

[0064] By comparison, it can be found that the cationic aqueous solution of Example 1 and the water-in-water-in-water emulsion prepared under the emulsification conditions have good emulsification properties, and can also effectively achieve sustained release and graded release of the drug, greatly improving the bioavailability of the drug.

[0065] This application uses the synergistic effect of chitosan and anionic polysaccharides without the use of any emulsifier to prepare a stable water-in-water-in-water emulsion with high stability and excellent biocompatibility. The positive charge of chitosan is combined with the negative charge on the gastric mucosa to enhance the retention time of particles in the stomach. The unique particle structure of the emulsion combined with the charge conversion mechanism can regulate drugs, achieve sustained release, and prolong the duration of drug effect. The charge conversion characteristics enable the particles to control the charge through pH changes in the gastrointestinal tract, thereby enhancing the adhesion of the particles in the stomach and achieving sustained release of drugs in the gastrointestinal tract, optimizing the delivery efficiency of the drug.

[0066] It should be understood that the application of the present application is not limited to the above examples. For ordinary technicians in this field, improvements or changes can be made according to the above description, and all these improvements and changes should fall within the scope of protection of the present application.

Claims

1. A method for preparing a water-in-water-in-water emulsion for drug delivery, characterized in that: The following steps are involved: preparing an anionic polysaccharide aqueous solution, and dissolving the drug in the anionic polysaccharide aqueous solution to obtain a mixed solution; preparing a cationic polysaccharide aqueous solution or a protein aqueous solution; The mixed solution is added into the cationic polysaccharide aqueous solution or the protein aqueous solution, mixed and then emulsified to obtain the water-in-water-in-water emulsion for drug delivery.

2. The method for preparing the water-in-water-in-water emulsion for drug delivery according to claim 1, characterized in that: The concentration of the anionic polysaccharide in the mixed solution is 0.25%-2.0%; The concentration of the cationic polysaccharide aqueous solution or protein aqueous solution is 0.25%-2.0%.

3. The method for preparing the water-in-water-in-water emulsion for drug delivery according to claim 2, characterized in that: The concentration of the anionic polysaccharide in the mixed solution is the same as the concentration of the cationic polysaccharide aqueous solution, and the volume ratio of the mixed solution to the cationic polysaccharide aqueous solution is 1:1.2; Or the concentration of the anionic polysaccharide in the mixed solution is the same as the concentration of the protein aqueous solution, and the volume ratio of the mixed solution to the protein aqueous solution is 1:1.

2.

4. The method for preparing the water-in-water-in-water emulsion for drug delivery according to claim 3, characterized in that: The emulsification method is one of high shear emulsification, ultrasonic treatment and high pressure homogenization.

5. The method for preparing the water-in-water-in-water emulsion for drug delivery according to claim 4, characterized in that: The emulsification method is high-pressure homogenization, the rotation speed is 10000-20000 rpm, and the processing time is 30s-3min.

6. The method for preparing the water-in-water-in-water emulsion for drug delivery according to claim 1, characterized in that: The concentration of the drug in the mixed solution is 0.1-2 mg / ml, and the drug is one of amoxicillin, levofloxacin and clarithromycin.

7. The method for preparing the water-in-water-in-water emulsion for drug delivery according to claim 1, characterized in that: The anionic polysaccharide is one or more of sodium hyaluronate, sodium alginate, sodium carboxymethyl cellulose, xanthan gum and carrageenan.

8. The method for preparing the water-in-water-in-water emulsion for drug delivery according to claim 1, characterized in that: The cationic polysaccharide is one or more of chitosan, polyethyleneimine, and poly(dimethyldiallylammonium chloride); The protein is one of gelatin, whey protein and soy protein isolate.

9. A water-in-water-in-water emulsion for drug delivery, characterized in that The invention is prepared by the method for preparing the water-in-water-in-water emulsion for drug delivery according to any one of claims 1 to 8.

10. A use of the water-in-water-in-water emulsion for drug delivery according to claim 9, characterized in that: The water-in-water-in-water emulsion for drug delivery is applied to drug delivery.

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