Soluble microneedle drug delivery system with adhesive backing and preparation method of soluble microneedle drug delivery system

Abstract

The invention relates to the technical field of micro-needle drug loading and releasing, in particular to a soluble micro-needle drug delivery system with an adhesive backing and a preparation method thereof.The micro-needle drug delivery system comprises a micro-needle tip and a backing part, and a micro-needle acts on a periodontal pocket, so that on one hand, the tip can rapidly dissolve and release loaded drugs; and on the other hand, the hydrogel backing layer with adhesion not only can be used for loading medicines to achieve the purpose of treatment, but also can be used for realizing the adhesion of the periodontal pocket and the dental surface, so that a favorable environment is provided for tooth tissue regeneration, the medicine delivery efficiency is enhanced, the treatment effect is improved, and the clinical treatment requirement of periodontitis is better met. The composite microneedle drug delivery system provided by the invention has double advantages of the microneedle and the hydrogel, realizes effective delivery of the drug at the periodontal part, is used for treating periodontitis, and has a wide application prospect.

Description

Technical Field

[0001] The invention relates to the technical field of microneedle drug-carrying and releasing technology, and in particular to a soluble microneedle drug delivery system with an adhesive backing and a preparation method thereof. Background Art

[0002] Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11% worldwide. The results of the Fourth National Oral Health Survey show that the prevalence of periodontal disease in the 35-65 age group is as high as 90%-95%. Periodontitis is a chronic inflammatory disease caused by bacterial infection, which mainly affects the gums, periodontal ligament and alveolar bone. Due to the persistence of bacterial infection and the overactive host immune response, alveolar bone absorption causes loose teeth and loss; at the same time, patients with periodontitis face long-term chronic inflammation, which makes treatment complicated.

[0003] Traditional periodontal treatments include non-surgical cleaning and scaling, i.e., removing plaque and tartar from the tooth surface, surgical treatments such as mechanical scaling, and local and systemic antibiotic treatments. Although these methods are effective, the oral cavity is a dynamic environment, often accompanied by functional movements such as pronunciation and chewing. In some severe cases, it is difficult to completely remove bacteria in deep lesions, and may be accompanied by problems such as antibiotic resistance and systemic side effects. Therefore, the current treatment methods are difficult to achieve transepidermal delivery of drugs to deep tissues.

[0004] Microneedles have been widely used in drug delivery systems, mainly intradermal delivery, and have a wide range of functions, making them an ideal strategy to overcome the many challenges in oral mucosal drug delivery system barriers. Microneedles can be made of various materials in different geometric shapes and different sizes, with sufficient mechanical strength to pierce the physical barrier of the skin to reach a specific depth of the tissue. At the same time, microneedles have the advantage of precise drug delivery. They can penetrate the gingival surface with less penetration force and deliver drugs directly to the periodontal lesion area, reducing drug waste, avoiding adverse reactions caused by systemic administration, and reducing patients' pain and discomfort.

[0005] In the prior art, there have been some related studies on microneedles. For example, patent technology document CN108186550A discloses a swellable polymer microneedle with controllable drug release rate, which includes a microneedle backing layer and a microneedle arranged on the microneedle backing layer. The microneedle backing layer is composed of PEGDA and a photoinitiator HMP, and the microneedle is composed of PEGDA, a photoinitiator HMP, PVP and a released drug. In this invention, the drug can be gradually released from the microneedle material, and there is a controllable drug release rate. However, during the occurrence of periodontitis, the loss of periodontal ligament attachment can lead to loose teeth. Therefore, during the drug administration process for periodontitis, it is best to achieve adhesion between the periodontal pocket and the tooth surface to fix the teeth and better exert the therapeutic effect of the drug on periodontitis.

[0006] Therefore, according to the above-mentioned related technologies, it is urgent to develop a soluble microneedle drug delivery system with an adhesive backing and a preparation method thereof. Summary of the invention

[0007] In view of this, the purpose of the present invention is to provide a soluble microneedle drug delivery system with an adhesive backing and a preparation method thereof, so as to solve the problem of periodontitis and the resulting loose teeth in the prior art.

[0008] The invention provides a soluble microneedle drug delivery system with an adhesive backing and a preparation method thereof.

[0009] A soluble microneedle drug delivery system with an adhesive backing, the microneedle drug delivery system comprising a microneedle tip and a backing portion;

[0010] The microneedle tip contains a tip solution;

[0011] The needle tip solution is prepared from a drug and a stabilizer;

[0012] The backing portion is a hydrogel;

[0013] The hydrogel is a modified hyaluronic acid hydrogel;

[0014] The modified hyaluronic acid hydrogel is prepared from hyaluronic acid and dopamine.

[0015] Preferably, the preparation method of the modified hyaluronic acid hydrogel is as follows:

[0016] Step A1. Add hyaluronic acid to a phosphate buffered saline solution of pH=5, stir until the hyaluronic acid is completely dissolved, add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide, place in a 37°C water bath and stir for 12 hours, then add dopamine under nitrogen protection and stir for 12 hours to obtain a mixture A;

[0017] Step A2. Place mixture A in a dialysis bag with a cutoff of 3300-3600Da and perform stirring dialysis for 70-73h, followed by freeze drying to obtain a hyaluronic acid-dopamine solid;

[0018] Step A3. Add the hyaluronic acid-dopamine solid to a phosphate buffered saline solution at pH = 9, stir until completely dissolved, and then add a sodium periodate aqueous solution. After 10-12 hours, a modified hyaluronic acid hydrogel is obtained.

[0019] Preferably, the phosphate buffered saline solution in step A1 is prepared from deionized water, sodium dihydrogen phosphate, disodium hydrogen phosphate and sodium hydroxide;

[0020] The dosage ratio of the phosphate buffered saline solution, hyaluronic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N-hydroxysuccinimide and dopamine is 28-33 mL: 490-510 mg: 240-247 mg: 143-150 mg: 245-253 mg.

[0021] Preferably, the freeze-drying temperature in step A2 is -83-78°C and the time is 23-25h;

[0022] The phosphate buffered saline solution in step A3 is prepared from deionized water, sodium dihydrogen phosphate, disodium hydrogen phosphate and sodium hydroxide.

[0023] Preferably, the concentration of the sodium periodate aqueous solution in step A3 is 45-50 mg / mL;

[0024] The dosage ratio of the hyaluronic acid-dopamine solid, the phosphate buffered saline solution and the sodium periodate aqueous solution is 10 mg: 3-5 mL: 45-50 μL.

[0025] Preferably, the drug is at least one of an antibiotic and a miRNA.

[0026] Preferably, the stabilizer is any one of sucrose, chitosan, glucose and trehalose, which serves as a needle tip protection material and can quickly release the drug during administration.

[0027] A method for preparing a soluble microneedle drug delivery system with an adhesive backing comprises the following steps:

[0028] Step S1. Add a stabilizer to deionized water to prepare solution A, and add a drug to solution A to obtain a needle tip solution;

[0029] Step S2. Add 200 μL of needle tip solution to each microneedle mold to cover all the pinholes, and cover the surface with a thin sheet, evacuate for 25-33 minutes, then remove the thin sheet, suck off the excess solution on the mold, and continue to evacuate for 110-130 minutes;

[0030] Step S3. Add 480-510 μL of hydrogel to each mold, evacuate for 4-5 hours, and then dry to obtain a soluble microneedle drug delivery system with an adhesive backing.

[0031] Preferably, the concentration of solution A in step S1 is 300-330 mg / mL;

[0032] The volume ratio of the solution A to the drug is 10:10-13.

[0033] Preferably, the drying temperature in step S3 is 40-45° C. and the drying time is 23-25 ​​h.

[0034] Beneficial effects of the present invention:

[0035] The present invention provides a soluble microneedle drug delivery system with an adhesive backing and a preparation method thereof. The microneedle drug delivery system of the present invention comprises a microneedle tip and a backing portion. By applying the microneedle to the periodontal pocket, the tip quickly releases the drug, and the adhesive hydrogel timely seals the periodontium, thereby providing a favorable environment for periodontal tissue regeneration, enhancing drug delivery efficiency, and improving treatment effects, thereby better meeting the clinical treatment needs of periodontitis and providing a new drug delivery method for local drug treatment of periodontitis. Compared with the prior art, the present invention has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings in the following description are only for the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0037] Figure 1 Schematic diagram of the steps for preparing the soluble microneedle drug delivery system with an adhesive backing in the present invention;

[0038] Figure 2 The present invention is a preparation process of the modified hyaluronic acid hydrogel (HA-DA);

[0039] Figure 3 is the nuclear magnetic spectrum of the modified hyaluronic acid hydrogel (HA-DA) prepared in the present invention;

[0040] Figure 4 The adhesion of the modified hyaluronic acid hydrogel (HA-DA) prepared in the present invention on the surfaces of different materials;

[0041] Figure 5 The effect of different concentrations of sucrose solution on drug distribution;

[0042] Figure 6 The effect of sucrose solution with different concentrations on the mechanical strength of microneedles;

[0043] Figure 7 The microneedles prepared in the present invention quickly dissolve at room temperature;

[0044] Figure 8 The drug loading of the microneedles prepared in the present invention;

[0045] Fig. 9 The distribution of different therapeutic drugs in the microneedles prepared in the present invention under a stereo fluorescence microscope;

[0046] Fig.10 This is the effect of different therapeutic drugs added in the present invention on the mechanical strength of the microneedle. DETAILED DESCRIPTION

[0047] In order to make the objectives, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with specific embodiments.

[0048] The sources and properties of some of the raw materials used in the present invention are as follows:

[0049] 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.; N-hydroxysuccinimide was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.; dopamine was purchased from Henan Puhui Tiancheng Biotechnology Co., Ltd.; hyaluronic acid was purchased from Hebei Chuangzhiyuan Biotechnology Co., Ltd.; sodium periodate was purchased from Hubei Changao Pharmaceutical Co., Ltd.; sodium dihydrogen phosphate was purchased from Suzhou Shangma Chemical Technology Co., Ltd.; disodium hydrogen phosphate was purchased from Hubei Huizepu Pharmaceutical Technology Co., Ltd.; sucrose was purchased from Lincang Nanhua Sugar Co., Ltd.; doxycycline was purchased from Hubei Zhongbo Lvya Biotechnology Co., Ltd.; miRNA nanoparticles were purchased from Wuhan Jinkairui Bioengineering Co., Ltd.

[0050] Example 1: A method for preparing a soluble microneedle drug delivery system with an adhesive backing, comprising the following steps:

[0051] S1. Add 490 mg of hyaluronic acid to 28 mL of phosphate buffered saline solution with a pH of 5, stir until the hyaluronic acid is completely dissolved, add 240 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 143 mg of N-hydroxysuccinimide, place in a 37° C. water bath and stir for 12 h, then add 245 mg of dopamine under nitrogen protection and stir for 12 h to obtain a mixture A;

[0052] S2. Place the mixture A in a dialysis bag with a cutoff of 3300Da and dialyze for 70 hours, then freeze-dry at -78°C for 23 hours to obtain a hyaluronic acid-dopamine solid;

[0053] S3. 10 mg of hyaluronic acid-dopamine solid was added to 3 mL of pH = 9 phosphate buffer solution, stirred until completely dissolved, and then 45 μL of 45 mg / mL sodium periodate aqueous solution was added. After 10 hours, a modified hyaluronic acid hydrogel was obtained;

[0054] S4. Add sucrose to deionized water to prepare solution A with a concentration of 300 mg / mL, and add 10 mL of doxycycline to 10 mL of solution A to obtain a needle tip solution;

[0055] S5. Add 200 μL of needle tip solution to each microneedle mold to cover all the pinholes, and cover the surface with a thin sheet, evacuate for 25 minutes, then remove the thin sheet, suck off the excess solution on the mold, and continue to evacuate for 110 minutes;

[0056] S6. Add 480 μL of modified hyaluronic acid hydrogel to each mold, evacuate for 4 hours, and then dry at 40° C. for 23 hours to obtain a soluble microneedle drug delivery system with an adhesive backing.

[0057] Example 2: A method for preparing a soluble microneedle drug delivery system with an adhesive backing, comprising the following steps:

[0058] S1. Add 495 mg of hyaluronic acid to 30 mL of phosphate buffered saline solution with a pH of 5, stir until the hyaluronic acid is completely dissolved, add 2402 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 145 mg of N-hydroxysuccinimide, place in a 37° C. water bath and stir for 12 h, then add 248 mg of dopamine under nitrogen protection and stir for 12 h to obtain a mixture A;

[0059] S2. Place the mixture A in a dialysis bag with a cutoff of 3400Da and dialyze for 71 hours, then freeze-dry at -80°C for 24 hours to obtain a hyaluronic acid-dopamine solid;

[0060] S3. 10 mg of hyaluronic acid-dopamine solid was added to 4 mL of pH = 9 phosphate buffer solution, stirred until completely dissolved, and then 48 μL of 48 mg / mL sodium periodate aqueous solution was added. After 11 hours, a modified hyaluronic acid hydrogel was obtained;

[0061] S4. Add trehalose to deionized water to prepare a solution A with a concentration of 320 mg / mL, and add 11 mL of doxycycline to 10 mL of solution A to obtain a needle tip solution;

[0062] S5. Add 200 μL of needle tip solution to each microneedle mold to cover all the pinholes, and cover the surface with a thin sheet, evacuate for 28 minutes, then remove the thin sheet, suck off the excess solution on the mold, and continue to evacuate for 120 minutes;

[0063] S6. Add 490 μL of modified hyaluronic acid hydrogel to each mold, evacuate for 4.5 hours, and then dry at 43° C. for 24 hours to obtain a soluble microneedle drug delivery system with an adhesive backing.

[0064] Example 3: A method for preparing a soluble microneedle drug delivery system with an adhesive backing, comprising the following steps:

[0065] S1. Add 500 mg of hyaluronic acid to 32 mL of phosphate buffered saline solution with a pH of 5, stir until the hyaluronic acid is completely dissolved, add 245 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 148 mg of N-hydroxysuccinimide, place in a 37° C. water bath and stir for 12 h, then add 250 mg of dopamine under nitrogen protection and stir for 12 h to obtain a mixture A;

[0066] S2. Place the mixture A in a dialysis bag with a cutoff of 3500Da and dialyze for 72 hours, then freeze-dry at -82°C for 24 hours to obtain a hyaluronic acid-dopamine solid;

[0067] S3. 10 mg of hyaluronic acid-dopamine solid was added to 4 mL of pH = 9 phosphate buffer solution, stirred until completely dissolved, and then 48 μL of 48 mg / mL sodium periodate aqueous solution was added. After 11 hours, a modified hyaluronic acid hydrogel was obtained;

[0068] S4. Glucose was added to deionized water to prepare a solution A with a concentration of 320 mg / mL, and 12 mL of miRNA nanoparticles were added to 10 mL of solution A to obtain a needle tip solution;

[0069] S5. Add 200 μL of needle tip solution to each microneedle mold to cover all the pinholes, and cover the surface with a thin sheet, evacuate for 30 minutes, then remove the thin sheet, suck off the excess solution on the mold, and continue to evacuate for 125 minutes;

[0070] S6. Add 500 μL of modified hyaluronic acid hydrogel to each mold, evacuate for 4.5 hours, and then dry at 43° C. for 24.5 hours to obtain a soluble microneedle drug delivery system with an adhesive backing.

[0071] Example 4: A method for preparing a soluble microneedle drug delivery system with an adhesive backing, comprising the following steps:

[0072] S1. Add 510 mg of hyaluronic acid to 33 mL of phosphate buffered saline solution with a pH of 5, stir until the hyaluronic acid is completely dissolved, add 247 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 150 mg of N-hydroxysuccinimide, place in a 37° C. water bath and stir for 12 h, then add 253 mg of dopamine under nitrogen protection and stir for 12 h to obtain a mixture A;

[0073] S2. Place the mixture A in a dialysis bag with a cutoff of 3600Da and dialyze for 73 hours with stirring, and then freeze-dry at -83°C for 25 hours to obtain a hyaluronic acid-dopamine solid;

[0074] S3. 10 mg of hyaluronic acid-dopamine solid was added to 5 mL of pH = 9 phosphate buffered saline solution, stirred until completely dissolved, and then 50 μL of 50 mg / mL sodium periodate aqueous solution was added. After 12 hours, a modified hyaluronic acid hydrogel was obtained;

[0075] S4. chitosan was added to deionized water to prepare a solution A with a concentration of 330 mg / mL, and 13 mL of a mixture of doxycycline and miRNA nanoparticles was added to 10 mL of solution A, wherein the volume ratio of doxycycline to miRNA nanoparticles was 1:1, to obtain a needle tip solution;

[0076] S5. Add 200 μL of needle tip solution to each microneedle mold to cover all the pinholes, and cover the surface with a thin sheet, evacuate for 33 minutes, then remove the thin sheet, suck off the excess solution on the mold, and continue to evacuate for 130 minutes;

[0077] S6. Add 510 μL of modified hyaluronic acid hydrogel to each mold, evacuate for 5 hours, and then dry at 45°C for 25 hours to obtain a soluble microneedle drug delivery system with an adhesive backing.

[0078] Comparative Example 1:

[0079] Compared with Example 1, this comparative example only replaces the "modified hyaluronic acid hydrogel" with the "hyaluronic acid hydrogel", and the remaining steps and parameters are the same, which will not be repeated in this comparative example. Finally, a soluble microneedle drug delivery system with an adhesive backing is obtained.

[0080] Depend on Figure 4 It can be seen that the modified hyaluronic acid hydrogel prepared in Example 1 of the present invention has good adhesion properties on the surfaces of skin tissue, glass and steel materials, and can adhere not only to flat surfaces but also to convex surfaces such as joints, indicating that the modified hyaluronic acid hydrogel has good adhesion properties and the ability to seal the periodontium; Fig.10It can be seen that the microneedle prepared in the present invention has strong mechanical strength, while the mechanical strength of the hyaluronic acid hydrogel itself is poor, which will affect the puncture performance and stability of the microneedle, that is, the comprehensive performance of Comparative Example 1 is worse than that of Example 1.

[0081] Comparative Example 2:

[0082] Compared with Example 1, this comparative example only replaces "solution A with a concentration of 300 mg / mL" with "solution A with a concentration of 100 mg / mL", and the remaining steps and parameters are the same, which will not be repeated in this comparative example. Finally, a soluble microneedle drug delivery system with an adhesive backing is obtained.

[0083] Comparative Example 3:

[0084] Compared with Example 1, this comparative example only replaces "solution A with a concentration of 300 mg / mL" with "solution A with a concentration of 600 mg / mL", and the remaining steps and parameters are the same, which will not be repeated in this comparative example. Finally, a soluble microneedle drug delivery system with an adhesive backing is obtained.

[0085] Depend on Figure 5 and Figure 6 It can be seen that when the sucrose concentration is 100 mg / mL, although the mechanical strength can reach the minimum force to pierce the skin barrier, the drug is only distributed at the top of the needle tip, and a good therapeutic effect cannot be achieved; when the sucrose concentration is 600 mg / mL, the mechanical strength reaches the highest, but the drug distribution is consistent with that when the concentration is 300 mg / mL, and is completely distributed throughout the entire needle tip, which can achieve a better therapeutic effect, but will cause unnecessary waste. Therefore, the preferred sucrose concentration is 300 mg / mL, which can not only achieve the required mechanical strength, but also ensure that the entire needle tip is loaded with drugs, that is, the comprehensive performance of Comparative Examples 2 and 3 is worse than that of Example 1.

[0086] like Figure 8As shown, a series of doxycycline solutions of different concentrations (10 μg / mL, 20 μg / mL, 30 μg / mL, 50 μg / mL, 100 μg / mL, 200 μg / mL) were prepared as standard solutions, and the absorbance at 280 nm of each concentration was detected. A first-order fit was performed to obtain the equation of concentration and absorbance: Conc. = (49.492) x Abs + (-7.2083). After that, the drug-containing needle tip of the prepared soluble microneedle patch was dissolved and the absorbance at 280 nm was detected. The concentration of the obtained needle tip solution was calculated in the equation, and the drug content of each microneedle patch was finally obtained. In the present invention, the needle tip drug loading of five microneedle patches was detected, and the average amount of antibiotics loaded on each microneedle was 198.7724 μg. The RNA content of each microneedle tip after dissolution was detected by a micro-ultraviolet-visible spectrophotometer, and the final average amount of miRNA loaded per piece was 2.19 μg, which indicates that the microneedles prepared in the present invention have a high drug loading capacity.

[0087] like Figure 7 As shown, the microneedles were placed at room temperature, and a microscope was used to record the dissolution of the microneedles in water at different time points (0, 5, 15, 30, 45, 60, 90, 120, 150, and 180 seconds). The data showed that the tips of the microneedles prepared in the present invention were basically completely dissolved within 3 minutes, but the microneedle substrates were basically not dissolved, indicating that the prepared soluble microneedles can achieve the effect of rapid dissolution of the tips and release of drugs.

[0088] like Fig. 9 As shown in FIG, the co-localization observation of doxycycline and miRNA nanoparticles loaded in the microneedle was performed by stereo fluorescence microscopy, and it can be seen that miRNA and doxycycline are mainly concentrated in the needle tip and are evenly distributed; Fig.10 As shown, the mechanical strength of the microneedles loaded with different drugs was tested. Regardless of whether doxycycline or miRNA nanoparticles were added, the mechanical strength of the microneedles was similar to that of the blank microneedles, and there was no significant change, that is, the microneedles prepared in the present invention had good mechanical strength.

[0089] Those skilled in the art should understand that the discussion of any of the above embodiments is merely illustrative and is not intended to imply that the scope of the present invention is limited to these examples. Under the concept of the present invention, the technical features in the above embodiments or different embodiments may be combined, the steps may be implemented in any order, and there are many other variations of the different aspects of the present invention as described above, which are not provided in detail for the sake of simplicity.

[0090] The present invention is intended to cover all such substitutions, modifications and variations that fall within the broad scope of the appended claims. Therefore, any omissions, modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A soluble microneedle drug delivery system with an adhesive backing, characterized in that: The microneedle drug delivery system comprises a microneedle tip and a backing portion; The microneedle tip contains a tip solution; The needle tip solution is prepared from a drug and a stabilizer; The backing portion is a hydrogel; The hydrogel is a modified hyaluronic acid hydrogel; The modified hyaluronic acid hydrogel is prepared from hyaluronic acid and dopamine.

2. The soluble microneedle drug delivery system with an adhesive backing according to claim 1, characterized in that: The preparation method of the modified hyaluronic acid hydrogel is as follows: Step A1. Add hyaluronic acid to a phosphate buffered saline solution of pH=5, stir until the hyaluronic acid is completely dissolved, add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide, place in a 37°C water bath and stir for 12 hours, then add dopamine under nitrogen protection and stir for 12 hours to obtain a mixture A; Step A2. Place mixture A in a dialysis bag with a cutoff of 3300-3600Da and perform stirring dialysis for 70-73h, followed by freeze drying to obtain a hyaluronic acid-dopamine solid; Step A3. Add the hyaluronic acid-dopamine solid to a phosphate buffered saline solution at pH = 9, stir until completely dissolved, and then add a sodium periodate aqueous solution. After 10-12 hours, a modified hyaluronic acid hydrogel is obtained.

3. The soluble microneedle drug delivery system with an adhesive backing according to claim 2, characterized in that: The phosphate buffered saline solution in step A1 is prepared from deionized water, sodium dihydrogen phosphate, disodium hydrogen phosphate and sodium hydroxide; The dosage ratio of the phosphate buffered saline solution, hyaluronic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N-hydroxysuccinimide and dopamine is 28-33 mL: 490-510 mg: 240-247 mg: 143-150 mg: 245-253 mg.

4. The soluble microneedle drug delivery system with an adhesive backing according to claim 2, characterized in that: The freeze drying in step A2 is performed at a temperature of -83-78°C and a time of 23-25 ​​hours; The phosphate buffered saline solution in step A3 is prepared from deionized water, sodium dihydrogen phosphate, disodium hydrogen phosphate and sodium hydroxide.

5. The soluble microneedle drug delivery system with an adhesive backing according to claim 2, characterized in that: The concentration of the sodium periodate aqueous solution in step A3 is 45-50 mg / mL; The dosage ratio of the hyaluronic acid-dopamine solid, the phosphate buffered saline solution and the sodium periodate aqueous solution is 10 mg: 3-5 mL: 45-50 μL.

6. The soluble microneedle drug delivery system with an adhesive backing according to claim 1, characterized in that: The drug is at least one of an antibiotic and a miRNA.

7. The soluble microneedle drug delivery system with an adhesive backing according to claim 1, characterized in that: The stabilizer is any one of sucrose, chitosan, glucose and trehalose.

8. A method for preparing a soluble microneedle drug delivery system with an adhesive backing according to any one of claims 1 to 7, characterized in that: The following steps are involved: Step S1. Add a stabilizer to deionized water to prepare solution A, and add a drug to solution A to obtain a needle tip solution; Step S2. Add 200 μL of needle tip solution to each microneedle mold to cover all the pinholes, and cover the surface with a thin sheet, evacuate for 25-33 minutes, then remove the thin sheet, suck off the excess solution on the mold, and continue to evacuate for 110-130 minutes; Step S3. Add 480-510 μL of hydrogel to each mold, evacuate for 4-5 hours, and then dry to obtain a soluble microneedle drug delivery system with an adhesive backing.

9. The method for preparing a soluble microneedle drug delivery system with an adhesive backing according to claim 8, characterized in that: The concentration of solution A in step S1 is 300-330 mg / mL; The volume ratio of the solution A to the drug is 10:10-13.

10. The method for preparing a soluble microneedle drug delivery system with an adhesive backing according to claim 8, characterized in that: The drying temperature in step S3 is 40-45° C. and the drying time is 23-25 ​​h.

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