An NPs hydrogel containing semaglutide and a preparation method thereof

Abstract

The present application discloses an NPs hydrogel containing semaglutide and a preparation method thereof, relating to the technical field of polymer composite materials, including the main drug, polylactic acid nanoparticles, dodecyl-modified hydroxypropyl methylcellulose, and PBS; wherein the polylactic acid nanoparticles are prepared by wrapping graphene with polyethylene glycol-polylactic acid, the main drug is semaglutide, the concentration of semaglutide in the hydrogel is 2-20 mg / ml, and the weight percentage of the polylactic acid nanoparticles and dodecyl-modified hydroxypropyl methylcellulose is 1-2 wt% of dodecyl-modified hydroxypropyl methylcellulose and 10 wt% of polylactic acid nanoparticles; it can achieve a long-term sustained and controlled release effect; and the degradation rates of the nanoparticles wrapped with graphene oxide and the nanoparticles not wrapped with graphene oxide are inconsistent, enabling further control of the drug release rate.

Description

Technical Field

[0001] The present invention relates to the technical field of polymer composites, and particularly relates to an NPs hydrogel containing semaglutide and a preparation method thereof. Background Art

[0002] A gel is a material with a three-dimensional network structure, which is commonly present in people's production and life, and has extensive research and applications especially in the fields of bioengineering and medicine. This material is usually a three-dimensional polymer network formed by polymer chains, which can absorb and retain a large amount of water or biological body fluids, and at the same time does not dissolve in water due to physical and chemical cross-linking effects. The hydrogel material formed by hydrophilic polymers shows thermodynamic compatibility when exposed to water, that is, it can swell in an aqueous medium, and has been widely used in fields such as drug controlled release, sensors, and tissue engineering.

[0003] Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) analogue, which has 94% sequence homology with human GLP-1. It promotes insulin secretion in a glucose concentration-dependent manner by activating the GLP-1 receptor, inhibits glucagon secretion, thereby regulating blood glucose levels. At the same time, semaglutide can also delay gastric emptying, increase satiety, reduce appetite and energy intake, thereby achieving the effect of weight loss.

[0004] For example, in a Chinese patent with the application number CN202110331349.3, a composite drug-loaded gel and a preparation method thereof are disclosed. The preparation method includes the steps: S1, adding pyrrole and dopamine hydrochloride into water and mixing evenly, then adding ammonium persulfate, stirring and reacting, and centrifuging and washing to obtain a polypyrrole-polydopamine nanocomposite; S2, placing the nanocomposite in a 1 mol / L hydrochloric acid solution containing drug molecules and an aqueous solution of graphene oxide in sequence, and centrifuging and adsorbing to obtain a graphene oxide-polypyrrole-polydopamine nanocomposite drug-loaded material; S3, mixing the nanocomposite drug-loaded material with a water-soluble polymer solution, adding a calcium chloride solution, stirring and then standing to obtain the composite drug-loaded gel. The composite drug-loaded material provided by this invention is combined with a water-soluble polymer, which can promote the formation of the composite drug-loaded gel, slow down the burst release phenomenon in the initial stage of drug release, and at the same time the composite drug-loaded gel has multiple stimulus responses.

[0005] However, for diabetic patients, there is still a need for improvement to achieve a long-term sustained and controlled release effect. Summary of the Invention

[0006] By providing an NPs hydrogel containing semaglutide and a preparation method thereof in the embodiments of the present application, the problems of insufficient compliance of diabetic patients and insufficient drug sustained and controlled release ability in the prior art are solved, and a longer sustained release time is achieved.

[0007] The embodiments of the present application provide an NPs hydrogel containing semaglutide, which includes the main drug, polylactic acid nanoparticles, dodecyl-modified hydroxypropyl methylcellulose, and PBS; wherein the polylactic acid nanoparticles are prepared by wrapping graphene with polyethylene glycol-polylactic acid.

[0008] Further, the main drug is semaglutide, and the concentration of semaglutide in the hydrogel is 2 - 20 mg / ml.

[0009] Further, the weight percentage of polylactic acid nanoparticles and dodecyl-modified hydroxypropyl methylcellulose is 1 - 2 wt% of dodecyl-modified hydroxypropyl methylcellulose and 10 wt% of polylactic acid nanoparticles.

[0010] Further, in the polylactic acid nanoparticles, the weight percentage of graphene oxide is 10 wt%.

[0011] The preparation method of the above NPs hydrogel containing semaglutide specifically includes: S1. Disperse graphene oxide powder in DMF or PBS and make it uniformly dispersed by ultrasonic treatment;

[0012] S2. Under the protection of inert gas, mix polyethylene glycol, L-lactide and a catalyst evenly; at the same time, slowly add the dispersed graphene oxide solution to the copolymer reaction system while stirring;

[0013] wherein the mass ratio of polyethylene glycol to L-lactide is 1:(2 - 9);

[0014] S3. Heat the reaction system to 110 - 130 °C and stir and react for 16 - 24 h to polymerize polyethylene glycol and L-lactide to form a polyethylene glycol-polylactic acid block copolymer, and wrap graphene oxide inside the copolymer during this process; dissolve the polyethylene glycol-polylactic acid block copolymer in DMSO and drop it into water under high-speed stirring to form a nanoparticle suspension; centrifuge and purify, and re-suspend in PBS to obtain a nanoparticle solution;

[0015] S4. Mix the semaglutide solution with the nanoparticle solution, wrap semaglutide into the nanoparticles, and adsorb semaglutide with graphene oxide; filter out the nanoparticles

[0016] S5. Prepare a 1 - 2 wt% dodecyl-modified hydroxypropyl methylcellulose solution; during use, add nanoparticles to the dodecyl-modified hydroxypropyl methylcellulose solution and stir evenly to obtain an NPs hydrogel containing semaglutide.

[0017] Further, the nanoparticle hydrogel is used for treatment by subcutaneous injection, and the dosage is adjusted according to the condition.

[0018] Furthermore, the particle size of the nanoparticles is 30 - 200 nm; the monolayer sheet diameter of the graphene oxide used is not greater than 200 nm; and the oxygen content is 30%.

[0019] When further filtering and screening the nanoparticles, the particles with a particle size greater than 200 nm are also subjected to secondary screening to screen out large nanoparticles with a size of 200 - 300 nm, and they are mixed with the already screened nanoparticles for use. The nanoparticles obtained from the secondary screening are large nanoparticles, and those obtained from the first screening are small nanoparticles. The mass ratio of the large nanoparticles to the small nanoparticles is 1:14.

[0020] Furthermore, the uncoated graphene oxide is directly mixed into the dodecyl-modified hydroxypropyl methylcellulose after loading semaglutide in the same manner as the nanoparticles.

[0021] The particle size of the graphene oxide is less than 200 nm; the mass ratio of the uncoated graphene oxide to the coated graphene oxide is 1:9.

[0022] Furthermore, the graphene oxide is also subjected to roughening treatment, specifically including heavy roughening, medium roughening, and light roughening.

[0023] Heavy roughening is specifically as follows: chemical etching is carried out using sulfuric acid with a concentration of 95%, and the reaction time is 0.5 - 1 h.

[0024] Medium roughening is specifically as follows: chemical etching is carried out using sulfuric acid with a concentration of 75%, and the reaction time is 0.5 - 1 h.

[0025] Light roughening is specifically as follows: ultrasonic treatment at 20 kHz for 0.5 - 1.

[0026] The coated graphene oxide and the uncoated graphene oxide are used in combination with different roughening treatments.

[0027] One or more technical solutions provided in the embodiments of the present application have at least the following technical effects or advantages:

[0028] First, graphene oxide has a large specific surface area and abundant oxygen-containing functional groups, which can effectively adsorb semaglutide molecules, thereby fixing them in nanoparticles, slowing down the release rate of semaglutide, and achieving a sustained and controlled release effect; and increasing the drug loading capacity of the nanoparticles to prevent large changes in the in-vivo drug concentration caused by the initial burst release; as part of the nanoparticles, graphene oxide enhances the structural stability of the hydrogel, and its lamellar structure and good dispersibility form a denser and more stable hydrogel network, increasing the retention time of the hydrogel in the human body; graphene oxide has good biocompatibility and degradability, which makes the hydrogel containing it safer and more sustainable in the human body. Over time, graphene oxide will gradually degrade, simultaneously releasing semaglutide to achieve a long-term sustained and controlled release effect; and the degradation rates of the nanoparticles wrapped with graphene oxide and those without graphene oxide are inconsistent, enabling further control of the drug release rate.

[0029] Second, due to their relatively large particle sizes, large nanoparticles have a relatively small specific surface area, and the rate of drug release from the particles will be relatively slow. In contrast, small nanoparticles have a relatively fast drug release rate. Therefore, the mixed use of nanoparticles with different particle sizes can achieve a dual drug release mechanism, that is, the combination of rapid release and slow release; the already-wrapped graphene oxide nanoparticles: due to being wrapped with polyethylene glycol-polylactic acid, these particles have a relatively large particle size and form a relatively stable skeleton structure in the hydrogel, and the drug release is relatively slow, which is conducive to achieving long-term sustained and controlled release.

[0030] Third, since the particle size of the unwrapped graphene oxide is less than 200 nm, the graphene oxide particles directly loaded with semaglutide can release the drug faster, providing an initial drug concentration peak, enabling the rapid achievement of the required drug concentration and making the in-vivo drug concentration controllable in the initial stage. Subsequently, the already-wrapped nanoparticles maintain a relatively low but stable drug concentration.

[0031] Fourth, heavy roughening significantly increases the drug loading capacity because the high specific surface area provides more binding sites. However, it also easily leads to an increase in the initial drug release because surface defects and roughness may accelerate the dissolution and release of the drug; medium roughening: while increasing the drug loading capacity, it relatively gently controls the drug release rate. Medium roughening is more suitable for drug delivery systems that require a medium release rate; light roughening: mainly increases the surface roughness through physical vibration, which helps the uniform adsorption and slow release of the drug; the graphene oxide wrapped with nanoparticles makes the rough treatment affect the sustained and controlled release process of the entire hydrogel, while the unwrapped ones mainly affect the initial release. Detailed implementation methods

[0032] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the technical field to which this invention belongs; the terms used in the specification of this invention are only for the purpose of describing specific embodiments and are not intended to limit this invention; the term "and / or" used herein includes any and all combinations of one or more of the related listed items.

[0033] Example 1

[0034] A NPs hydrogel for containing semaglutide in this application specifically includes: active pharmaceutical ingredient, polylactic acid nanoparticles, dodecyl-modified hydroxypropyl methylcellulose, PBS; wherein the polylactic acid nanoparticles are prepared by wrapping graphene with polyethylene glycol-polylactic acid.

[0035] The active pharmaceutical ingredient is semaglutide, and the concentration of semaglutide in the hydrogel is 2-20 mg / ml.

[0036] The weight percentage of polylactic acid nanoparticles and dodecyl-modified hydroxypropyl methylcellulose is 1-2 wt% of dodecyl-modified hydroxypropyl methylcellulose and 10 wt% of polylactic acid nanoparticles.

[0037] In the polylactic acid nanoparticles, the weight percentage of graphene oxide is 10 wt%.

[0038] The preparation method of the above-mentioned NPs hydrogel of semaglutide is as follows:

[0039] S1. Disperse graphene oxide powder in DMF or PBS and make it uniformly dispersed by ultrasonic treatment.

[0040] S2. Under the protection of inert gas, mix polyethylene glycol, L-lactide and catalyst evenly; at the same time, slowly add the dispersed graphene oxide solution into the copolymer reaction system while stirring.

[0041] Wherein the mass ratio of polyethylene glycol to L-lactide is 1:(2-9).

[0042] S3. Heat the reaction system to 110-130 °C and stir and react for 16-24 h to polymerize polyethylene glycol and L-lactide to form a polyethylene glycol-polylactic acid block copolymer, and wrap graphene oxide inside the copolymer during this process; dissolve the polyethylene glycol-polylactic acid block copolymer in DMSO and drop it into water under high-speed stirring to form a nanoparticle suspension; centrifuge and purify, and re-suspend in PBS to obtain a nanoparticle solution.

[0043] After filtration, the particle size of the nanoparticles is 30-200 nm; the monolayer sheet diameter of the graphene oxide used is not more than 200 nm; the oxygen content is 30%.

[0044] S4. Mix the semaglutide solution with the nanoparticle solution, encapsulate semaglutide into the nanoparticles, and adsorb semaglutide using graphene oxide; filter out the nanoparticles.

[0045] S5. Prepare a 1 - 2 wt% solution of dodecyl - modified hydroxypropyl methylcellulose; when in use, add the nanoparticles to the dodecyl - modified hydroxypropyl methylcellulose solution and stir evenly to obtain the NPs hydrogel containing semaglutide.

[0046] This nanoparticle hydrogel is used for treatment by subcutaneous injection, and the dosage is adjusted according to the condition.

[0047] The technical solutions in the embodiments of the present application at least have the following technical effects or advantages:

[0048] Graphene oxide has a large specific surface area and abundant oxygen - containing functional groups, which can effectively adsorb semaglutide molecules, thus fixing them in the nanoparticles, slowing down the release rate of semaglutide, achieving a sustained - release and controlled - release effect; and increasing the drug loading capacity of the nanoparticles, preventing large changes in the in - vivo drug concentration caused by the initial burst release; as a part of the nanoparticles, graphene oxide enhances the structural stability of the hydrogel, and its lamellar structure and good dispersibility form a denser and more stable hydrogel network, increasing the retention time of the hydrogel in the human body.

[0049] Graphene oxide has good biocompatibility and degradability, which makes the hydrogel containing it safer and more sustainable in the human body. Over time, graphene oxide will gradually degrade while releasing semaglutide, achieving a long - term sustained - release and controlled - release effect; and the degradation rates of the nanoparticles encapsulated with graphene oxide and those without graphene oxide are inconsistent, enabling further control of the drug release rate.

[0050] Due to the enhancement of graphene oxide, the retention time of the hydrogel in the human body is significantly prolonged, ensuring that semaglutide can be continuously released at the target site, improving the treatment effect; the adsorption of graphene oxide enables semaglutide to be released from the hydrogel in a slower and more controllable manner, maintaining a stable drug concentration in the body, reducing side effects, and improving patient compliance; by prolonging the retention time and achieving the sustained - release and controlled - release effect, the hydrogel containing graphene oxide can improve the bioavailability of semaglutide. Due to the longer retention time, the achieved sustained - release and controlled - release effect, and the improved bioavailability, the semaglutide NPs hydrogel containing graphene oxide can significantly improve the treatment effect.

[0051] The sustained and controlled release effect helps to reduce the peak concentration and fluctuation of the drug, thereby reducing the incidence and severity of side effects; since the drug release is more stable and has a long duration, patients can receive treatment more conveniently, improving compliance.

[0052] In some embodiments, when polyethylene glycol: L-lactide = 1:2, the content of L-LA in the polylactic acid nanoparticles is relatively high, resulting in a relatively high degradation rate of the nanoparticles; for short-term drug delivery, in the treatment of diseases that require rapid onset but do not want continuous drug administration for too long, such as acute diseases or short-term management;

[0053] The cumulative release amount of the hydrogel prepared by this method within 48 h in an environment of pH 7.4 is 32%; the cumulative release amount within 14 d is 68%;

[0054] In some embodiments, polyethylene glycol: L-lactide = 1:5, which can balance the drug release rate and duration; can stably release the drug for a long time, reduce the dosing frequency, and improve patient compliance;

[0055] The cumulative release amount of the hydrogel prepared by this method within 48 h in an environment of pH 7.4 is 28%; the cumulative release amount within 14 d is 58%;

[0056] In some embodiments, polyethylene glycol: L-lactide = 1:9; it is suitable for long-term drug administration management to ensure stable drug release for a long time;

[0057] The cumulative release amount of the hydrogel prepared by this method within 48 h in an environment of pH 7.4 is 24%; the cumulative release amount within 14 d is 53%.

[0058] Example Two

[0059] The above-mentioned embodiments are further improved on the basis of Example One by adding graphene oxide to the hydrogel to increase the stability of the hydrogel and reduce the initial burst release, and to increase the drug loading capacity of the nanoparticles and reduce the direct effect of the free drug.

[0060] When filtering and screening the nanoparticles, the particles with a particle size greater than 200 nm are also secondarily screened, and the large nanoparticles with a size of 200 - 300 nm are screened out and mixed with the already screened nanoparticles. The secondarily screened nanoparticles are large nanoparticles, and the first-screened ones are small nanoparticles. The mass ratio of the large nanoparticles to the small nanoparticles is 1:14.

[0061] The technical solutions in the embodiments of the present application at least have the following technical effects or advantages:

[0062] Due to their relatively large particle sizes, large nanoparticles have a relatively small specific surface area, and the rate at which drugs are released from the particles is relatively slow. In contrast, small nanoparticles have a relatively fast drug release rate. Therefore, the combined use of nanoparticles with different particle sizes can achieve a dual drug release mechanism, namely, the combination of rapid release and slow release;

[0063] The distribution and arrangement of large and small nanoparticles in the hydrogel are different, which affects the overall structure and stability of the hydrogel. Large particles form a more stable skeletal structure, while small particles may fill the voids between large particles, thereby enhancing the density and stability of the hydrogel and also helping to regulate the drug release rate;

[0064] Due to the combined use of large and small nanoparticles, the retention time of the hydrogel in the human body may be extended. The stable skeleton formed by large particles and the filling effect of small particles together enhance the structural stability of the hydrogel, making it more difficult to be cleared by the organism;

[0065] By adjusting the ratio of large and small nanoparticles, the drug release rate and time can be more precisely controlled, enabling the drug to be released in a more stable manner over a longer period of time, thereby improving the therapeutic effect and reducing side effects;

[0066] Since the drug release is more stable and has a longer duration, the therapeutic effect will be significantly improved. By precisely controlling the drug release rate and time, the peak concentration and fluctuations of the drug are reduced, thereby lowering the incidence and severity of side effects; Since the drug release is more stable and has a longer duration, patients can receive treatment more conveniently without frequent drug administration or dose adjustment, thereby improving compliance.

[0067] In this embodiment, polyethylene glycol: L-lactide = 1:5 is taken as an example;

[0068] The cumulative release amount of the hydrogel prepared by this method within 48 h in an environment with a pH of 7.4 is 23%; the cumulative release amount within 14 d is 51%.

[0069] Example Three

[0070] Example Two reduces free drug molecules through nanoparticles with different particle sizes. For the sustained and controlled release needs of different patients, it is further improved on the basis of Example Two.

[0071] Unencapsulated graphene oxide is loaded with semaglutide by the same method as the nanoparticles and then directly mixed into dodecyl-modified hydroxypropyl methylcellulose;

[0072] The particle size of graphene oxide is less than 200 nm; the mass ratio of unencapsulated graphene oxide to encapsulated graphene oxide is 1:9.

[0073] The technical solutions in the embodiments of the present application at least have the following technical effects or advantages:

[0074] Encapsulated graphene oxide nanoparticles: Due to being encapsulated by polyethylene glycol - polylactic acid, these particles have a relatively large particle size, form a relatively stable skeleton structure in the hydrogel, and the drug release is relatively slow, which is beneficial to achieving long - term sustained and controlled release;

[0075] Unencapsulated graphene oxide has a particle size less than 200 nm. Graphene oxide particles directly loaded with semaglutide can release the drug faster, providing an initial drug concentration peak, enabling the rapid attainment of the required drug concentration, making the initial in - vivo drug concentration controllable, and then the encapsulated nanoparticles maintain a relatively low but stable drug concentration.

[0076] Graphene oxide has an extremely high specific surface area. Whether encapsulated or not, it can effectively adsorb semaglutide molecules. Unencapsulated graphene oxide shows stronger drug adsorption ability due to the presence of a large number of oxygen - containing functional groups on its surface, further affecting its release characteristics;

[0077] The addition of graphene oxide can enhance the mechanical strength and stability of the hydrogel. Graphene oxide sheets can form physical or chemical cross - links with polymer chains in the hydrogel matrix, thereby prolonging the retention time of the hydrogel in the body;

[0078] By combining the use of encapsulated and unencapsulated graphene oxide, a dual drug release mode is achieved; initially, unencapsulated GO rapidly releases the drug, providing an immediate therapeutic effect; subsequently, the encapsulated GO nanoparticles continuously release the drug at a slower rate, maintaining the therapeutic effect;

[0079] The addition of graphene oxide enhances the structural stability of the hydrogel and prolongs its retention time in the body. At the same time, by precisely controlling the particle size distribution and encapsulation state of GO, a more precise sustained and controlled release effect is achieved; the dual release mode ensures the effective concentration of the drug in the body, meeting both the initial treatment requirements and ensuring long - term efficacy maintenance;

[0080] The extended retention time and stable controlled release effect enable patients to reduce the dosing frequency, improve the convenience of treatment and patient compliance; by controlling the drug release rate and concentration fluctuation, the potential harm of the drug peak concentration to the body can be reduced, and the occurrence of side effects can be minimized.

[0081] In this embodiment, polyethylene glycol: L - lactide = 1:5 is taken as an example;

[0082] The cumulative release amount of the hydrogel prepared by this method is 17% within 24 hours and 28% within 48 hours in an environment with pH 7.4; the cumulative release amount within 14 days is 58%.

[0083] Example 4

[0084] In Example 3, the initial binding and release of the hydrogel were controlled by whether graphene oxide was encapsulated. To increase the loading amount and improve the utilization rate, further improvements were made on the basis of Example 3.

[0085] The graphene oxide was also subjected to rough treatment, specifically including heavy roughness, medium roughness, and light roughness;

[0086] Heavy roughness specifically: Chemical etching was carried out using sulfuric acid with a concentration of 95%, and the reaction time was 0.5 - 1 h;

[0087] Medium roughness specifically: Chemical etching was carried out using sulfuric acid with a concentration of 75%, and the reaction time was 0.5 - 1 h;

[0088] Light roughness specifically: Ultrasonic treatment at 20 kHz for 0.5 - 1;

[0089] The encapsulated graphene oxide and the unencapsulated graphene oxide were combined and used with different rough treatments;

[0090] The technical solutions in the above embodiments of the present application have at least the following technical effects or advantages:

[0091] Heavy rough treatment significantly increases the drug loading amount because the high specific surface area provides more binding sites. However, it also easily leads to an increase in the initial release of the drug because surface defects and roughness may accelerate the dissolution and release of the drug;

[0092] Medium roughness: While increasing the drug loading amount, it relatively gently controls the drug release rate. Medium rough treatment is more suitable for drug delivery systems that require a medium release rate;

[0093] Light roughness: Increasing the surface roughness through physical vibration helps the uniform adsorption and slow release of the drug;

[0094] The rough treatment of the graphene oxide encapsulated with nanoparticles affects the sustained and controlled release process of the entire hydrogel, while the unencapsulated one mainly affects the initial release;

[0095] For example, combination 1: Heavy rough unencapsulated GO + Light rough encapsulated GO;

[0096] Application scenario: Drug delivery system in rapid treatment;

[0097] Heavy and rough uncoated GO, due to its high specific surface area and rapid release characteristics, can be used for the initial rapid delivery of high concentrations of chemotherapy drugs to achieve rapid therapeutic effects. In contrast, light and rough coated GO can maintain a stable drug release for a longer time, reduce the rapid clearance of drugs in the body, and extend the treatment window.

[0098] In this embodiment, polyethylene glycol: L-lactide = 1:5 is taken as an example.

[0099] The cumulative release amount of the hydrogel prepared by this method is 23% within 24 hours and 32% within 48 hours in an environment with a pH of 7.4; the cumulative release amount within 14 days is 62%.

[0100] Combination 2: Heavy and rough coated GO + medium and rough uncoated GO

[0101] Application scenario: Insulin delivery in daily diabetes treatment

[0102] In diabetes management, it is necessary to simulate the natural insulin secretion pattern of the pancreas. Heavy and rough coated GO provides a relatively gentle but sustained insulin release to simulate basal insulin secretion; while medium and rough uncoated GO can quickly respond to elevated blood glucose after meals and provide pulsed insulin release to better control postprandial hyperglycemia.

[0103] In this embodiment, polyethylene glycol: L-lactide = 1:5 is taken as an example.

[0104] The cumulative release amount of the hydrogel prepared by this method is 14% within 24 hours and 25% within 48 hours in an environment with a pH of 7.4; the cumulative release amount within 14 days is 53%.

[0105] The above is only the preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention can have various changes and modifications. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included within the protection scope of the present invention.

Claims

1. A NPs hydrogel containing semaglutide, characterized in that, It includes the main drug, polylactic acid nanoparticles, dodecyl-modified hydroxypropyl methylcellulose, and PBS; among which, the polylactic acid nanoparticles are prepared by wrapping graphene with polyethylene glycol-polylactic acid, and the main drug is semaglutide; The preparation method of the hydrogel specifically includes: S1. Disperse the graphene oxide powder in DMF or PBS and make it uniformly dispersed by ultrasonic treatment; S2. Under the protection of inert gas, mix polyethylene glycol, L-lactide and a catalyst evenly; at the same time, slowly add the dispersed graphene oxide solution to the copolymer reaction system while stirring; wherein, the mass ratio of polyethylene glycol to L-lactide is 1:(2-9); S3. Heat the reaction system to 110-130 °C and stir and react for 16-24 h to polymerize polyethylene glycol and L-lactide to form a polyethylene glycol-polylactic acid block copolymer, and wrap the graphene oxide inside the copolymer during this process; dissolve the polyethylene glycol-polylactic acid block copolymer in DMSO and drop it into water under high-speed stirring to form a nanoparticle suspension; centrifuge and purify, and resuspend it in PBS to obtain a nanoparticle solution; S4. Mix the semaglutide solution with the nanoparticle solution, wrap semaglutide into the nanoparticles, and adsorb semaglutide with graphene oxide; filter and screen out the nanoparticles; The filtration and screening is a secondary screening. First, screen out small nanoparticles with a size of 30-200 nm, and then screen out large nanoparticles with a size of 200-300 nm. The large nanoparticles and the small nanoparticles are used in combination, and the mass ratio of the large nanoparticles to the small nanoparticles is 1:14; S5. Prepare a 1-2 wt% dodecyl-modified hydroxypropyl methylcellulose solution and mix it with the nanoparticles and unencapsulated graphene oxide filtered and screened in the step S4 to obtain an NPs hydrogel containing semaglutide; The unencapsulated graphene oxide loads semaglutide in the same method as the nanoparticles filtered and screened in the step S4; the mass ratio of the unencapsulated graphene oxide to the encapsulated graphene oxide is 1:9; The graphene oxide is subjected to rough treatment, specifically including heavy roughing, medium roughing, and light roughing; different rough treatments are used for the encapsulated graphene oxide and the unencapsulated graphene oxide; The heavy roughing is specifically: chemically etch with 95% concentrated sulfuric acid for a reaction time of 0.5-1 h; The medium roughing is specifically: chemically etch with 75% concentrated sulfuric acid for a reaction time of 0.5-1 h; The light roughing is specifically: perform ultrasonic treatment at 20 kHz for 0.5-1.

2. The NPs hydrogel containing semaglutide according to claim 1, wherein The concentration of semaglutide in the hydrogel is 2-20 mg / ml.

3. The NPs hydrogel for semaglutide according to claim 1, characterized in that, The polylactic acid nanoparticles and dodecyl-modified hydroxypropyl methylcellulose are 1-2 wt% dodecyl-modified hydroxypropyl methylcellulose and 10 wt% polylactic acid nanoparticles by weight percentage.

4. The NPs hydrogel containing semaglutide according to claim 2, wherein In the polylactic acid nanoparticles, the weight percentage of graphene oxide is 10 wt%.