Drug-loaded embolization microspheres and preparation method thereof

Abstract

The application belongs to the technical field of medical devices, and particularly discloses a drug-carryable embolization microsphere and a preparation method thereof. The drug-carryable embolization microsphere contains an amphiphilic structure. The amphiphilic structure refers to a polymer containing both a hydrophobic chain segment and a hydrophilic chain segment. The hydrophilic chain segment in the amphiphilic structure is at least one of polyethylene glycol, alginate and chitosan, and the hydrophobic chain segment is at least one of polyoxypropylene, polylactic acid, polyglycolic acid and polycaprolactone. The amphiphilic structure is derived from an amphiphilic macromonomer with a carbon-carbon double bond functional group. Due to the introduction of the hydrophobic structure of the amphiphilic macromolecule, the microsphere can resist swelling caused by excessive water absorption, and can maintain a stable physical size without shrinkage after adsorbing a hydrophobic drug. In addition, the hydrophobicity of the microsphere can improve the adsorption amount and release rate of the drug, and compared with mainstream drug-carryable embolization microspheres, the microsphere has better anti-deformation performance and drug delivery performance.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medical devices, and particularly relates to a drug-loaded embolization microsphere and a preparation method thereof. BACKGROUND

[0002] Hepatocellular carcinoma is one of cancers. Surgical resection is a commonly used treatment method, but surgery may not be suitable for patients with advanced tumors, and trans-catheter arterial chemo-embolization (TACE) is the preferred method of non-surgical treatment. The principle is to use medical imaging equipment such as digital subtraction angiography (DSA) to guide the catheter to reach the tumor site in the human body through the artery, and then to inject anti-tumor drugs and embolic agents through the catheter to block the blood supply of the tumor tissue, so as to make the tumor shrink and necrose in a short time. The tumor embolic agent plays a key role in TACE, and the latest generation of drug-loaded embolization microspheres (DEB) are used to inject the drug-containing microspheres into the blood supply artery of the tumor tissue through the superselective vascular catheter, which not only blocks the blood supply source needed for tumor cell proliferation, but also continuously releases anticancer drugs to the tumor target area, which is more targeted than directly injecting iodine oil containing tumor drugs, has less toxic and side effects on other organs of the body, and can improve the quality of life of patients with advanced liver cancer, prolong the survival period, and reduce the toxic and side effects of the whole body.

[0003] The mainstream drug-loaded embolization microspheres on the market, such as polyvinyl alcohol drug-loaded microspheres such as DC Beads, Hepaspheres, and Callispheres, which have been commercialized, change in size after loading drugs. This is mainly because the drugs, such as epirubicin and irinotecan, are hydrophobic drugs, and when they are adsorbed into the microspheres by electrostatic attraction, the microspheres will change in swelling rate due to the dramatic change in hydrophilicity and hydrophobicity, ultimately leading to a change in the size of the microspheres. According to the size of the tumor and the physical condition of the patient, the dose of the drug used in the clinic is different for each patient, which leads to different changes in the size of the drug-loaded microspheres. For patients who need a high dose of medication, the microspheres have a high deformation rate after loading drugs, and the highest change can be more than 30%. The shrunken microspheres with too small a particle size can easily cause ectopic embolization such as pulmonary embolism, which greatly limits the clinical use and the effect of vascular embolization. SUMMARY

[0004] The present application provides a drug-loaded embolization microsphere, which solves the problem of unstable structure and large deformation after loading drugs of the drug-loaded microsphere in the prior art, and realizes a relatively stable physical form structure.

[0005] The application provides a drug-loaded embolization microsphere, which contains an amphiphilic structure, wherein the amphiphilic structure refers to a polymer containing a hydrophobic chain segment and a hydrophilic chain segment; the hydrophilic chain segment is at least one of polyethylene glycol, alginate and chitosan, preferably polyethylene glycol; the hydrophobic chain segment is at least one of polyoxypropylene, polylactic acid, polyglycolic acid and polycaprolactone, preferably polyoxypropylene; the amphiphilic structure is derived from an amphiphilic macromonomer with a carbon-carbon double bond functional group; thus, the drug-loaded embolization microsphere can be formed by polymerization and crosslinking of the amphiphilic macromonomer with a carbon-carbon double bond functional group and a drug-loaded monomer with a carbon-carbon double bond functional group under the action of a photoinitiator and ultraviolet light; the drug-loaded embolization microsphere can also be formed by polymerization and crosslinking of the amphiphilic macromonomer with a carbon-carbon double bond functional group, a hydrophilic macromonomer with a carbon-carbon double bond functional group and a drug-loaded monomer with a carbon-carbon double bond functional group under the action of a photoinitiator and ultraviolet light; the particle size of the microsphere ranges from 1 to 1000 um.

[0006] Further, the hydrophilic macromonomer with a carbon-carbon double bond functional group is preferably polyethylene glycol diacrylate PEGDA.

[0007] Further, the amphiphilic macromonomer with a carbon-carbon double bond functional group is selected from poloxamer terminated by diacrylate and poloxamer terminated by diacrylamide. It should be noted that the poloxamer Poloxamer is a trade name Pluronic, which is a non-ionic surfactant, and its chemical formula is HO(C2H4O) a (C3H6O) b (C2H4O) c H; wherein the value range of a and c is 2-130, the value range of b is 15-67, and it is a polyoxyethylene polyoxypropylene ether block copolymer; the poloxamer is an amphiphilic macromolecule, which contains a hydrophobic chain segment polyoxypropylene and a hydrophilic chain segment polyoxyethylene, i.e., polyethylene glycol.

[0008] Further, the drug-loaded monomer with a carbon-carbon double bond functional group is 2-acrylamide-2-methylpropane sulfonic acid sodium or methacryl sulfonic acid.

[0009] By adjusting the kind and proportion of the hydrophilic segment and the hydrophobic segment in the drug-loadable embolization microspheres, the drug-loading or drug-releasing behavior of the hydrogel microspheres and the change in the physical size of the microspheres after drug loading can be regulated; the higher the proportion of the hydrophobic segment structure is, the more obvious the anti-swelling effect is, and the drug loading amount also increases; the hydrophobic segment of the present application is from polyoxypropylene, polylactic acid, polyglycolic acid, polycaprolactone structure, in addition to being able to provide hydrophobicity and good biocompatibility, since these materials belong to plastic materials, they have good mechanical properties, can increase the overall mechanical properties of the material, thereby ensuring the roundness of the prepared microspheres and the physical strength during use, reducing the microsphere rupture caused by the shearing action of injection, thereby avoiding the ectopic embolization reaction of the broken microspheres and the burst release reaction of the loaded drugs.

[0010] As a preferred embodiment, the drug-loadable embolization microspheres are prepared by the following steps:

[0011] Step S1, a double amphiphilic macromonomer containing a carbon-carbon double bond functional group, a drug-loadable monomer containing a carbon-carbon double bond functional group, and a photoinitiator are dissolved in water to prepare an aqueous phase;

[0012] Step S2, the aqueous phase is added to an oil phase containing a surfactant to perform an emulsification reaction to form a water-in-oil emulsion;

[0013] Step S3, ultraviolet light irradiation is applied to initiate a polymerization reaction;

[0014] Step S4, after the reaction is completed, the microspheres are subjected to solid-liquid separation and washing, and finally collected in physiological saline for preservation.

[0015] Further, the emulsification reaction in step S2 can be realized by a reaction kettle-mechanical stirring paddle device, a high-pressure homogenizer device, and a micro-channel device.

[0016] The present application also provides a drug-loadable embolization microsphere, which is obtained by mixing the above-mentioned drug-loadable embolization microspheres with a positively charged drug solution, so as to load the drug through ionization; the positively charged drug is selected from one or more of doxorubicin hydrochloride, irinotecan, epirubicin, mitoxantrone, epirubicin, gemcitabine, bleomycin, vinorelbine, and oxaliplatin.

[0017] The one or more technical solutions provided in the test examples of the present application have at least the following technical effects or advantages: The present application prepares a drug-loaded hydrogel microsphere containing an amphiphilic structure which can maintain stable physical size after drug loading, the drug loading rate can be regulated, and the hydrophobic structure in the hydrogel microsphere can improve the drug loading rate, the drug loading rate of epirubicin can reach 120mg / ml, which is higher than the epirubicin loading rate (20-40mg / ml) of the mainstream DEB products on the market such as DC Beads, Hepaspheres and Callispheres; and the release of the drug is also regulated by the hydrophobic structure, which can improve the release ratio of the drug, after adsorbing epirubicin, the highest drug release ratio can reach 50%, which is higher than the lower drug release ratio in the range of 10%-30% of the above mainstream DEB products on the market, and similar effects can be achieved for other hydrophobic drugs such as mitoxantrone, which can effectively improve the therapeutic effect of tumor drugs in TACE. BRIEF DESCRIPTION OF DRAWINGS

[0018] Figure 1 The microsphere diagram prepared for test group 4-1 in the test examples of the present application, the scale in the figure is 100um;

[0019] Figure 2 The polyethylene glycol hydrogel swelling rate test results of the four test groups in the test examples of the present application, from left to right in the figure are polyethylene glycol hydrogels after swelling test of test groups 1-3, 1-1, 1-4 and 1-2. DETAILED DESCRIPTION

[0020] In order to better understand the above technical solutions, the above technical solutions will be described in detail below in combination with the drawings of the specification and the specific embodiments.

[0021] The polyethylene glycol diacrylate (PEGDA), 2-acrylamide-2-methylpropanesulfonic acid sodium (AMPS) and Irgacure 2959 involved in the following test examples are purchased from Sigma; the poloxamer diacrylate (F127-DA) is purchased from EFL.

[0022] Test Example 1: Preparation and Swelling Rate Test of Polyethylene Glycol Hydrogel

[0023] The brief synthesis route of the polyethylene glycol hydrogel of the present experimental example is shown as follows:

[0024]

[0025] The present test example discloses the swelling rules of the corresponding hydrogel microspheres with the same chemical structure by preparing drug-loaded polyethylene glycol hydrogel blocks and studying their swelling conditions:

[0026] Step S101, four test groups are set, respectively, test group 1-1, test group 1-2, test group 1-3, test group 1-4, the raw material configuration of each test group is configured according to Table 1, respectively, and the polyethylene glycol diacrylate (PEGDA, Sigma) is dissolved in PBS, 2-acrylamide-2-methylpropane sulfonic acid sodium (AMPS, Sigma) and Irgacure2959 as a photoinitiator (Sigma);

[0027] Step S102, the solution prepared in step S101 is injected into the mold according to the fixed volume;

[0028] Step S103, curing: the solution is irradiated by ultraviolet lamp for 30 minutes to realize crosslinking and curing;

[0029] Step S104, collection: the gel is taken out and collected in physiological saline.

[0030] Swelling rate test of drug-loaded polyethylene glycol hydrogel:

[0031] The hydrogel prepared above is added to a 37℃ physiological saline solution for swelling equilibrium, and the size of the hydrogel is measured at 30 minutes to calculate the swelling rate.

[0032] Table 1

[0033] # PEGDA molecular weight PEGDA concentration AMPS concentration 2959 concentration Swelling ratio 1-1 700 5％ 1％ 0.1％ 42% (swollen and cracked) 1-2 700 5％ 3％ 0.1％ 46% (swollen and cracked) 1-3 40000 5％ 1％ 0.1％ 65％ 1-4 40000 5％ 3％ 0.1％ 62％

[0034] As Figure 2 The swelling rate test results of the polyethylene glycol hydrogel of the four test groups of the present test example are shown in the figure, from left to right in the figure are the polyethylene glycol hydrogels after swelling test of test groups 1-3, 1-1, 1-4 and 1-2.

[0035] From the above results, it can be seen that the polyethylene glycol hydrogel compounded with AMPS monomer will swell in physiological saline in a large proportion, and in test groups 1-1 and 1-2, the small molecular weight PEGDA macromonomer has a higher crosslinking density, and its hydrogel network structure has higher rigidity, and the swelling and cracking phenomenon occurs during the swelling process.

[0036] Test Example Two: Preparation and Swelling Rate Test of Poloxamer Hydrogel

[0037] The brief synthesis route of the poloxamer hydrogel of the present test example is shown as follows:

[0038]

[0039]

[0040] This test example is to prepare poloxamer hydrogel and study its swelling behavior to embody the swelling law of the corresponding hydrogel microspheres with the same chemical structure:

[0041] Step S201, set four test groups, respectively, test group 2-1, test group 2-2, test group 2-3, test group 2-4, the raw material configuration of each test group is configured according to Table 2, according to Table 2, dissolve poloxamer diacrylate F127-DA (EFL), PEGDA, 2-acrylamide-2-methylpropane sulfonic acid sodium (AMPS) and photoinitiator Irgacure 2959 in PBS;

[0042] Step S202, inject the solution prepared in step S201 into the mold according to the fixed volume;

[0043] Step S203, curing: irradiate the solution with ultraviolet lamp for 30 minutes to realize crosslinking and curing;

[0044] Step S204, collection: take out the gel and collect it in normal saline.

[0045] Drug-loaded swelling rate:

[0046] The hydrogel gel prepared above is added to 37℃, 5ml of normal saline solution for swelling equilibrium, and the size of the hydrogel is measured at 30 minutes, and the swelling rate is calculated.

[0047] Table 2

[0048]

[0049] From the above results, it can be seen that the poloxamer hydrogel compounded with AMPS monomer has a smaller swelling rate in normal saline than the polyethylene glycol hydrogel in test example 1, and when more PEGDA is added to reduce the proportion of hydrophobic block (2-2, 2-4), the swelling rate rises, which embodies the anti-swelling function of hydrophobic block in the hydrogel network.

[0050] Test example three: preparation and drug release test of doxorubicin-loaded polyethylene glycol microspheres

[0051] The preparation of doxorubicin-loaded polyethylene glycol microspheres in this test example:

[0052] Step S301, aqueous phase: set four test groups, respectively, test group 3-1, test group 3-2, test group 3-3, test group 3-4, the raw material configuration of each test group is configured according to Table 3, according to Table 3, dissolve polyethylene glycol diacrylate (PEGDA), 2-acrylamide-2-methylpropane sulfonic acid sodium (AMPS) and photoinitiator Irgacure 2959 in PBS;

[0053] Step S302, oil phase: liquid paraffin containing 1% Span 80 was prepared and placed in mechanical stirring for continuous stirring;

[0054] Step S303, emulsification: at room temperature, the water phase was added to the continuously stirred oil phase, and stirred for 30 minutes;

[0055] Step S304, solidification: the emulsion was irradiated with ultraviolet lamp for 30 minutes to achieve cross-linking and solidification;

[0056] Step S305, washing and collection: the microspheres were separated from the liquid paraffin and washed with an aqueous solution containing 1% Tween 20, and the 100-300 um microspheres were sieved out by wet method and collected in physiological saline.

[0057] Step S306, drug loading: 1 ml of the above prepared 100-300 um hydrogel microspheres were taken, 6 ml of 20 mg / ml epirubicin physiological saline solution at 37°C was added for drug adsorption, and the concentration of epirubicin in the drug solution was measured at 30 minutes, 1 hour, 2 hours, 3 hours, and the drug adsorption amount was calculated.

[0058] Drug release test: the above drug-adsorbed microspheres were transferred to 37°C, 20 mL of physiological saline for drug release test, and the leaching liquid was replaced at 30 minutes, 1 hour, 2 hours, 3 hours, 24 hours, 48 hours, 72 hours, and the concentration of epirubicin in the leaching liquid was measured, and the cumulative drug release amount was calculated.

[0059] Table 3

[0060]

[0061] From the above results, it can be seen that the polyethylene glycol hydrogel microspheres compounded with AMPS monomers can adsorb epirubicin by electrostatic adsorption, and the drug loading amount increases with the increase of the AMPS monomer feeding ratio (increase of sulfonic acid group). The drug-loaded microspheres release the drug into the platform within 72 hr, with a low release ratio, the highest being only 16.8%, and most of the drug is locked inside the microspheres by strong electrostatic adsorption and is not released, affecting the bioavailability of the drug.

[0062] Test Example Four: Preparation of Epirubicin-loaded Poloxamer Microspheres and Drug Release Test

[0063] The preparation of epirubicin-loaded poloxamer microspheres in this test example:

[0064] Step S401, aqueous phase: six test groups, respectively, test group 4-1, test group 4-2, test group 4-3, test group 4-4, test group 4-5 and test group 4-6; the raw material configuration of each test group is configured according to Table 4 respectively; according to Table 4, dissolve poloxamer diacrylate (F127-DA), PEGDA, 2-acrylamide-2-methylpropane sulfonic acid sodium (AMPS) and photoinitiator Irgacure 2959 in PBS;

[0065] Step S402, oil phase: prepare liquid paraffin containing 1% Span 80, and place it in mechanical stirring for continuous stirring;

[0066] Step S403, emulsification: at room temperature, add the aqueous phase to the continuously stirred oil phase and stir for 30 minutes;

[0067] Step S404, curing: apply UV light to the emulsion for 30 minutes to achieve crosslinking and curing;

[0068] Step S405, washing and collection: separate the microspheres from the liquid paraffin, wash them with a 1% Tween 20 aqueous solution, sieve out the 100-300um microspheres by wet sieving, and collect them in physiological saline;

[0069] Step S406, drug loading: take 1ml of the 100-300um hydrogel microspheres prepared above, add 6ml of 20mg / ml epirubicin physiological saline solution at 37°C, and measure the concentration of epirubicin in the drug solution at 30 minutes, 1 hour, 2 hours, 3 hours, and calculate the drug adsorption amount.

[0070] Drug release test: transfer the above drug-adsorbed microspheres to 20mL of physiological saline at 37°C for drug release test, and replace the leaching liquid at 30 minutes, 1 hour, 2 hours, 3 hours, 24 hours, 48 hours, 72 hours, and measure the concentration of epirubicin in the leaching liquid, and calculate the cumulative drug release amount.

[0071] Table 4

[0072]

[0073]

[0074] From the above results, it can be seen that the poloxamer hydrogel microspheres compounded with AMPS monomers can adsorb more epirubicin through electrostatic attraction compared to Test Example 3, the drug loading increases with the increase of the AMPS monomer feeding ratio (sulfonic group increases), and the highest can reach 118.6 mg / ml. The drug-loaded microspheres release the drug into the platform within 72 hours, and the release ratio is higher than that of Test Example 3, which can reach about 50%. Compared with Test Groups 4-1 and 4-2 without additional addition of hydrophilic block PEGDA, when more hydrophilic block PEGDA is introduced into the microspheres, as shown in Test Groups 4-3, 4-4, 4-5, and 4-6, the drug loading of the microspheres decreases, but due to the presence of the hydrophobic block in poloxamer, the drug loading and drug release ratio are higher than those of the samples in Test Example 3.

[0075] Test Example Five: Preparation and Drug Release Test of Mitoxantrone-loaded Polyethylene Glycol Microspheres

[0076] The preparation of the mitoxantrone-loaded polyethylene glycol microspheres in this test example is as follows:

[0077] Step S501, aqueous phase: three test groups were set up, namely Test Group 5-1, Test Group 5-2, and Test Group 5-3; the raw material configuration of each test group was configured according to Table 5; according to Table 5, polyethylene glycol diacrylate (PEGDA), 2-acrylamide-2-methylpropanesulfonic acid sodium (AMPS), and photoinitiator Irgacure 2959 were dissolved in PBS;

[0078] Step S502, oil phase: liquid paraffin containing 1% Span 80 was prepared and placed in mechanical stirring for continuous stirring;

[0079] Step S503, emulsification: at room temperature, the water phase was added to the continuously stirred oil phase, and stirred for 30 minutes;

[0080] Step S504, curing: the emulsion was irradiated with a UV lamp for 30 minutes to achieve cross-linking and curing;

[0081] Step S505, washing and collection: the microspheres were separated from the liquid paraffin and washed with an aqueous solution containing 1% Tween 20, and the 100-300 um microspheres were sieved and collected in physiological saline.

[0082] Step S506, drug loading: 0.2 ml of the above prepared 100-300 um hydrogel microspheres were taken, 1 ml of 20 mg / ml mitoxantrone physiological saline solution was added at 37°C, and the concentration of mitoxantrone in the drug solution was measured at 30 minutes, 1 hour, 2 hours, and 3 hours to calculate the drug adsorption amount.

[0083] Drug release test: The above drug adsorbed microspheres were transferred to 10 mL of normal saline at 37°C for drug release test, and the extraction liquid was replaced at 30 minutes, 1 hour, 2 hours, 3 hours, 24 hours, 48 hours, 72 hours, and the concentration of mitoxantrone in the extraction liquid was measured to calculate the cumulative drug release amount.

[0084] Table 5

[0085]

[0086] As can be seen from the results of test groups 5-1 and 5-2, the drug loading capacity of polyethylene glycol microspheres increases with the increase of sulfonic group density, but the drug release rate decreases, which may be due to the increase of sulfonic group density increasing the adsorption of microspheres to mitoxantrone, making it difficult for the drug to be released from the hydrogel. As can be seen from the data of test group 5-3, the molecular weight of PEGDA also affects the adsorption and release of the drug, and the increase of the molecular weight of PEGDA will reduce the adsorption of the drug, and the cumulative release rate within 72 hours will also decrease.

[0087] Test Example Six: Preparation of Mitoxantrone-loaded Poloxamer Microspheres and Drug Release Test

[0088] Preparation of mitoxantrone-loaded in this test example:

[0089] Step S601, aqueous phase: six test groups, test group 6-1, test group 6-2, test group 6-3, test group 6-4, test group 6-5 and test group 6-6; the raw material configuration of each test group is configured according to Table 5; according to Table 6, dissolve poloxamer diacrylate F127-DA, PEGDA, 2-acrylamide-2-methylpropanesulfonic acid sodium AMPS and photoinitiator Irgacure 2959 in PBS;

[0090] Step S602, oil phase: prepare liquid paraffin containing 1% Span 80 and place it in mechanical stirring for continuous stirring;

[0091] Step S603, emulsification: at room temperature, add the aqueous phase to the continuously stirred oil phase and stir for 30 minutes;

[0092] Step S604, solidification: apply UV light to the emulsion for 30 minutes to achieve cross-linking and solidification;

[0093] Step S605, washing and collection: separate the microspheres from the liquid paraffin and wash them with an aqueous solution containing 1% Tween 20, sieve out the microspheres with a size of 100-300 um by wet sieving and collect them in normal saline.

[0094] Step S606, drug loading: take 0.2 ml of the prepared hydrogel microspheres, add 37℃, 1 ml of 20 mg / ml mitoxantrone physiological saline solution for drug adsorption, and measure the concentration of mitoxantrone in the drug solution at 30 minutes, 1 hour, 2 hours, 3 hours, and calculate the drug adsorption amount.

[0095] Drug release test: the above drug adsorbed microspheres are transferred to 37℃, 20mL of physiological saline for drug release test, and the leaching liquid is replaced at 30 minutes, 1 hour, 2 hours, 3 hours, 24 hours, 48 hours, 72 hours, and the concentration of mitoxantrone in the leaching liquid is measured, and the cumulative drug release amount is calculated.

[0096] Table 6

[0097]

[0098] From the above results, compared with test example 5, the introduction of poloxamer improves the hydrophobicity of the material, thereby significantly improving the cumulative release ratio of the drug at 72 hr, all of which can reach more than 90%. However, the introduction of hydrophobic structure has a certain reducing effect on the drug adsorption of mitoxantrone, among which, test group 6-5 can provide the highest drug loading capacity, reaching 14.9 mg.

Claims

1. A drug-loadable embolic microsphere, characterized in that, The drug-loadable embolic microspheres contain an amphiphilic structure, which refers to a polymer containing both hydrophobic and hydrophilic segments. The hydrophilic segment in the amphiphilic structure is derived from at least one of polyethylene glycol, alginate, and chitosan, while the hydrophobic segment is derived from at least one of polyoxypropylene, polylactic acid, polyglycolic acid, and polycaprolactone. The amphiphilic structure originates from an amphiphilic macromonomer containing carbon-carbon double bond functional groups. The drug-loadable embolic microspheres are formed by polymerizing and crosslinking an amphiphilic macromonomer containing carbon-carbon double bond functional groups with a drug-loadable monomer containing carbon-carbon double bond functional groups under the action of a photoinitiator and ultraviolet light; or the drug-loadable embolic microspheres are formed by polymerizing and crosslinking an amphiphilic macromonomer containing carbon-carbon double bond functional groups, a hydrophilic macromonomer containing carbon-carbon double bond functional groups, and a drug-loadable monomer containing carbon-carbon double bond functional groups under the action of a photoinitiator and ultraviolet light. The particle size of the drug-loadable embolic microspheres ranges from 1 to 1000 μm. The amphiphilic macromonomer containing carbon-carbon double bond functional groups is F127-DA; The drug-loadable monomer containing carbon-carbon double bond functional groups is sodium 2-acrylamide-2-methylpropanesulfonate or methylpropanesulfonic acid; The preparation method of the drug-loadable embolic microspheres includes the following steps: Step S1: Dissolve the amphiphilic macromonomer containing carbon-carbon double bond functional groups, the drug-loadable monomer containing carbon-carbon double bond functional groups, and the photoinitiator together in water to prepare an aqueous phase. Step S2: The aqueous phase is added to the oil phase containing the surfactant to carry out an emulsification reaction to form a water-in-oil emulsion; Step S3: Apply ultraviolet light to initiate the polymerization reaction; Step S4: After the reaction is complete, the microspheres are subjected to solid-liquid separation and washing, and finally collected and stored in physiological saline.

2. The drug-loadable embolic microsphere as described in claim 1, characterized in that, The hydrophilic macromonomer containing carbon-carbon double bond functional groups is polyethylene glycol diacrylate (PEGDA).

3. The method for preparing drug-loadable embolic microspheres according to any one of claims 1-2, characterized in that, The preparation method includes the following steps: Step S1: Dissolve the amphiphilic macromonomer containing carbon-carbon double bond functional groups, the drug-loadable monomer containing carbon-carbon double bond functional groups, and the photoinitiator together in water to prepare an aqueous phase. Step S2: The aqueous phase is added to the oil phase containing the surfactant to carry out an emulsification reaction to form a water-in-oil emulsion; Step S3: Apply ultraviolet light to initiate the polymerization reaction; Step S4: After the reaction is complete, the microspheres are subjected to solid-liquid separation and washing, and finally collected and stored in physiological saline.

4. The method for preparing drug-loadable embolic microspheres as described in claim 3, characterized in that, The photoinitiator is Irgacure2959.

5. The method for preparing drug-loadable embolic microspheres as described in claim 3, characterized in that, The emulsification reaction in step S2 is achieved by a reaction vessel-mechanical stirring device, a high-pressure homogenizer, or a microchannel device.

6. A drug-loaded embolic microsphere, characterized in that, The drug-loaded embolic microspheres are prepared by mixing the drug-loaded embolic microspheres as described in any one of claims 1-2 with a positively charged drug solution, i.e., by loading the drug-loaded embolic microspheres with a drug through ionization; the positively charged drug is selected from one or more of doxorubicin hydrochloride, irinotecan, epirubicin, mitoxantrone, cyproheptadine, gemcitabine, bleomycin, vinorelbine, and oxaliplatin.

7. The drug-loaded embolic microspheres as described in claim 6, characterized in that, The particle size of the drug-loaded embolized microspheres ranges from 100 to 300 μm.

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