Mesoporous bioactive glass drug-loaded microsphere preparation as well as preparation method and application thereof

Abstract

The invention relates to a mesoporous bioactive glass drug-loaded microsphere preparation as well as a preparation method and application thereof, the microsphere preparation takes mesoporous bioactive glass microspheres as a skeleton, and an anti-tumor drug is loaded on the mesoporous bioactive glass microspheres. The mesoporous bioactive glass microsphere comprises a SiO2-P2O5 binary oxide or a SiO2-CaO-P2O5 ternary oxide, has a mesoporous channel structure of 5-12 nm and a high specific surface area of 300-500 m < 2 > / g, and can be used for loading antitumor drugs with various characteristics. Compared with the prior art, the microspheres are combined with the bioglass degradability and alkaline degradation products to neutralize the tumor acid environment, and a better tumor interventional embolism treatment effect can be synergistically achieved. The mesoporous bioactive glass microspheres are prepared by adopting a microfluidic process, the method is simple and high in yield, and meanwhile, the purposes of regulating and controlling the size of the microspheres and the aperture of mesopores are achieved by regulating the flow rates of internal and external phases.

Description

Technical Field

[0001] The invention relates to the technical field of sustained-release drug preparation, and in particular to a mesoporous bioactive glass drug-loaded microsphere preparation and a preparation method and application thereof. Background Art

[0002] Mesoporous bioglass is widely used in many medical fields such as drug delivery and hard tissue engineering because of its uniform and adjustable nanopore structure, good biocompatibility and bioactivity. In particular, drug delivery systems based on mesoporous bioglass microspheres have great potential in transcatheter arterial chemoembolization (TACE). Compared with the problems of traditional embolic microspheres such as gelatin and polyvinyl alcohol, which are easy to deform after drug loading, uncontrollable drug loading, and difficult to adjust release kinetics, mesoporous bioglass microspheres have regular shapes. By regulating the size, composition and surface properties of the microspheres, efficient drug loading and in situ targeted release can be achieved. The drug release rate can be controlled by the mesoporous pore capacity, specific surface area and chemical groups of the mesoporous bioglass microspheres, thereby improving the therapeutic effect of TACE drugs and greatly reducing side effects. In addition, mesoporous bioglass microspheres can be gradually degraded in the body fluid environment, and the degradation products are alkaline. Their slow release can neutralize the excess lactic acid in the tumor microenvironment, thereby destroying the protection of lactic acid to the tumor, continuously accelerating tumor cell apoptosis, and enhancing the therapeutic effect of TACE.

[0003] Chinese patent CN102190428A discloses an ordered mesoporous microsphere drug carrier and a preparation method thereof. The patent uses microemulsion polymerization technology to prepare mesoporous bioactive glass microspheres containing oxides SiO2, CaO, and P2O3. However, the preparation process of this method is complicated, and the particle size of the prepared microspheres is difficult to accurately control, resulting in a wide particle size distribution of the microspheres, which is not conducive to drug release, thereby weakening the application effect of the drug-loaded microspheres. Summary of the invention

[0004] The purpose of the present invention is to provide a mesoporous bioactive glass drug-loaded microsphere preparation and its preparation method and application, and to prepare drug-loaded mesoporous bioactive glass microspheres with different sizes and pore sizes through a microfluidic process and use them for tumor embolization therapy.

[0005] The purpose of the present invention can be achieved by the following technical solutions:

[0006] In one aspect, the present invention provides a mesoporous bioactive glass drug-loaded microsphere preparation, wherein the microsphere preparation uses mesoporous bioactive glass microspheres as a skeleton on which anti-tumor drugs are loaded.

[0007] Preferably, the particle size of the mesoporous bioactive glass microspheres is adjustable and is between 150 and 450 μm.

[0008] Preferably, the mesoporous bioactive glass microspheres have a mesoporous structure, the mesopore diameter is adjustable, the mesopore diameter is 5 to 12 nm, and the specific surface area of ​​the mesoporous bioactive glass microspheres is 300 to 500 m 2 / g.

[0009] Preferably, the anti-tumor drug is loaded in the mesoporous channels of the mesoporous bioactive glass microspheres, the drug loading rate of the mesoporous bioactive glass microspheres is 2.12% to 2.70%, and the encapsulation rate is 72.05% to 92.61%.

[0010] Preferably, the mesoporous bioactive glass microspheres include SiO2-P2O5 binary oxide or SiO2-CaO-P2O5 ternary oxide.

[0011] Further preferably, when the mesoporous bioactive glass microspheres are SiO2-P2O5 binary oxides, the molar ratio of SiO2 to P2O5 is (70-90): (10-30).

[0012] Further preferably, when the mesoporous bioactive glass microspheres are SiO2-CaO-P2O5 ternary oxides, the molar ratio of SiO2, CaO and P2O5 is (70-90): (5-15): (5-15).

[0013] Preferably, the anti-tumor drug comprises one or more combinations of epirubicin, idarubicin, oxaliplatin, irinotecan, topotecan, sorafenib and catalase.

[0014] In a second aspect, the present invention further provides a method for preparing the above-mentioned mesoporous bioactive glass drug-loaded microsphere preparation, comprising the following preparation steps:

[0015] S1, weighing silicon, calcium, and phosphorus precursor compounds according to the molar ratio of each element in the mesoporous bioactive glass microspheres, using a nonionic surfactant as a structure directing agent, performing a sol-gel reaction under acidic conditions, and then obtaining a mesoporous bioactive glass precursor solution through an aging treatment;

[0016] S2. Using a microfluidic method, the mesoporous bioactive glass precursor solution obtained in step S1 is used as a dispersed internal phase and the oil phase is used as a continuous external phase to obtain monodisperse droplets, and then cross-linked in a receiving phase to prepare mesoporous bioactive glass microspheres;

[0017] S3, washing, drying, and calcining the mesoporous bioactive glass microspheres obtained in step S2 to remove the surfactant;

[0018] S4. Loading the anti-tumor drug into the mesoporous channels of the mesoporous bioactive glass microspheres obtained in step S4 after removing the surfactant by an impregnation method.

[0019] Preferably, in step S1, the silicon precursor compound is selected from one or more of tetramethylsilane and tetraethylsilane, the calcium precursor compound is selected from one or more of calcium nitrate and calcium chloride, and the phosphorus precursor compound is selected from triethyl phosphate.

[0020] Preferably, in step S1, the nonionic surfactant is selected from any one of the triblock copolymers P123, P108, F127, and F108.

[0021] Preferably, in step S1, the sol-gel reaction time is 12 to 48 hours, the aging time is 3 to 7 days, and the criterion for whether the aging is complete is that the mesoporous bioactive glass precursor solution can maintain transparency and drip shape when dripped into ammonia water.

[0022] Preferably, in step S1, the acidic condition refers to a pH between 1 and 2.

[0023] Preferably, in step S2, the oil phase is selected from any one of liquid paraffin, mineral oil, dimethyl silicone oil and n-heptane.

[0024] Preferably, in step S2, the flow rate of the inner phase is 0.001-0.05 mL / min, and the flow rate of the outer phase is 0.01-0.5 mL / min. The size of the monodisperse droplets is changed by adjusting the flow rates of the inner and outer phases to obtain microsphere products of different sizes.

[0025] Preferably, in step S2, the components of the receiving phase are the same as those of the continuous external phase and 8% to 20% by volume of aqueous ammonia is added, and the receiving phase is kept at a rotation speed of 30 to 70 rpm at 20°C to 25°C.

[0026] Preferably, in step S2, the microfluidic method uses a coaxial needle as a microfluidic reactor and a syringe pump as an output power device to build a microfluidic device.

[0027] Preferably, in step S3, the heating rate of the calcination treatment is 1-5°C / min, the calcination insulation temperature is 500-650°C, and the insulation time is 4-6h.

[0028] Preferably, in step S3, the washing refers to washing with anhydrous ethanol and petroleum ether alternately.

[0029] Preferably, in step S3, after removing the surfactant, the microsphere products with particle size distribution in different intervals can be further obtained by sieving.

[0030] Preferably, in step S4, the anti-tumor drug needs to be dissolved in a solvent to obtain an anti-tumor drug solution, which is then loaded into the mesoporous bioactive glass microspheres after the surfactant is removed by an impregnation method.

[0031] Further preferably, in step S4, the solvent is a phosphate buffer solution (pH=7.4), and the concentration of the anti-tumor drug solution is 0.1-3 mg / mL.

[0032] Preferably, step S4 further comprises placing the mesoporous bioactive glass microspheres loaded with anti-tumor drugs in a shaking incubator at 37° C. and shaking at a rate of 100-120 rpm for 18-30 hours, centrifuging the supernatant, and measuring the drug loading capacity of the microspheres after drying completely at 37° C.

[0033] In a third aspect, the present invention also provides a use of the above-mentioned mesoporous bioactive glass drug-loaded microsphere preparation in the preparation of tumor embolization therapeutic drugs.

[0034] Compared with the prior art, the present invention is not only simple to prepare, but also the synthesis size can be precisely controlled. The synthesized microspheres have a large specific surface area and can meet the needs of carrying a variety of drugs to achieve the expected sustained-release effect.

[0035] The present invention provides a new solution for the preparation of mesoporous bioactive glass microspheres by using microfluidic technology. Compared with the methods for preparing organic microspheres such as microemulsion polymerization in the prior art, the microfluidic preparation operation is simpler and highly automated, the process flow is clearer, and the size of the microspheres can be precisely controlled. The present invention can prepare uniform and monodisperse mesoporous bioactive glass microspheres by a microfluidic control method, the size of the microspheres can be controlled by changing the flow rate of the internal and external phases, and the anti-tumor drugs can be loaded into the mesoporous bioactive glass microspheres by an impregnation method, so as to be used for TACE treatment.

[0036] Compared with the prior art, the present invention has the following beneficial effects:

[0037] (1) The present invention provides a mesoporous bioactive glass drug-loaded microsphere preparation, which has a mesoporous bioactive glass microsphere skeleton and can load a variety of anti-tumor drugs. The prepared mesoporous bioactive glass microspheres have adjustable particle size and mesopore size and a high specific surface area. The microspheres can synergistically achieve better tumor interventional embolization treatment effects.

[0038] (2) The mesoporous bioactive glass microspheres prepared by the present invention have high specific surface area and pore volume, which are suitable for the lossless loading of various anti-tumor drugs. The drug loading capacity and release rate are adjustable, and the degradation products are alkaline at the same time. In the field of tumor embolization therapeutic drugs, they have the potential to neutralize lactic acid and synergize drugs for efficient and controllable treatment.

[0039] (3) The present invention adopts a microfluidic process to prepare mesoporous bioactive glass microspheres, which is simple and high-yield. At the same time, the size of the microspheres and the pore size of the mesopores are controlled by adjusting the flow rates of the internal and external phases. The prepared microspheres have the characteristics of high dispersibility, uniform size, and adjustable size.

[0040] (4) The raw materials used in the preparation method of the present invention are easily available, the synthesis method and the required equipment are simple, and the synthesis process is green and environmentally friendly. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 Field emission scanning electron microscope observation photos of mesoporous bioactive glass microspheres prepared in Examples 1 to 9 of the method of the present invention;

[0042] Figure 2 The particle size distribution diagram of the mesoporous bioactive glass microspheres prepared in Examples 1 to 9 of the method of the present invention;

[0043] Figure 3 This is a transmission electron microscope observation photograph of the mesoporous bioactive glass microspheres prepared in Example 1 of the method of the present invention;

[0044] Figure 4 The specific surface area of ​​the mesoporous bioactive glass microspheres prepared in Examples 1 to 9 of the method of the present invention is tested for N2 adsorption-desorption isotherms and pore size distribution;

[0045] Figure 5 The cumulative release percentage of epirubicin in different pH conditions of the mesoporous bioactive glass microspheres prepared in Examples 1 to 9 of the present invention. DETAILED DESCRIPTION

[0046] The present invention is described in detail below in conjunction with the accompanying drawings and specific embodiments. This embodiment is implemented based on the technical solution of the present invention, and provides a detailed implementation method and specific operation process, but the protection scope of the present invention is not limited to the following embodiments.

[0047] Unless otherwise specified, the reagents, methods, instruments and equipment used in the present invention are conventional reagents, methods, instruments and equipment in the art. Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0048] A mesoporous bioactive glass drug-loaded microsphere preparation, wherein the microsphere preparation uses mesoporous bioactive glass microspheres as a skeleton and is loaded with anti-tumor drugs. The particle size of the mesoporous bioactive glass microspheres is adjustable to 150-450 μm; the mesoporous bioactive glass microspheres have a mesoporous structure, the mesopore diameter is adjustable to 5-12 nm, and the specific surface area of ​​the mesoporous bioactive glass microspheres is 300-500 m 2 / g; the anti-tumor drug is loaded in the mesoporous channels of the mesoporous bioactive glass microspheres, the drug loading rate of the mesoporous bioactive glass microspheres is 2.12% to 2.70%, and the encapsulation rate is 72.05% to 92.61%. The mesoporous bioactive glass microspheres include SiO2-P2O5 binary oxide or SiO2-CaO-P2O5 ternary oxide. When the mesoporous bioactive glass microspheres are SiO2-P2O5 binary oxide, the molar ratio of SiO2 to P2O5 is (70 to 90): (10 to 30); when the mesoporous bioactive glass microspheres are SiO2-CaO-P2O5 ternary oxide, the molar ratio of SiO2 to CaO to P2O5 is (70 to 90): (5 to 15): (5 to 15). The anti-tumor drug comprises one or more combinations of epirubicin, idarubicin, oxaliplatin, irinotecan, topotecan, sorafenib and catalase.

[0049] The above-mentioned mesoporous bioactive glass drug-loaded microsphere preparation is prepared by the following preparation method:

[0050] S1. Weigh silicon, calcium and phosphorus precursor compounds according to the molar ratio of each element in the mesoporous bioactive glass microspheres, use a non-ionic surfactant as a structure directing agent, carry out a sol-gel reaction under acidic conditions, and then obtain a mesoporous bioactive glass precursor solution through aging treatment; wherein the silicon precursor compound is selected from one or more of tetramethylsilane and tetraethylsilane, the calcium precursor compound is selected from one or more of calcium nitrate and calcium chloride, and the phosphorus precursor compound is selected from triethyl phosphate; the non-ionic surfactant is selected from any one of the triblock copolymers P123, P108, F127, and F108; the sol-gel reaction time is 12 to 48 hours, and the aging time is 3 to 7 days.

[0051] S2. A microfluidic device is constructed using a coaxial needle as a microfluidic reactor and a syringe pump as an output power device. The mesoporous bioactive glass precursor solution obtained in step S1 is used as a dispersed internal phase and an oil phase as a continuous external phase. Monodisperse droplets are obtained through a microfluidic process, and mesoporous bioactive glass microspheres are prepared by cross-linking in a receiving phase; wherein the oil phase is selected from any one of liquid paraffin, mineral oil, dimethyl silicone oil, and n-heptane; the flow rate of the dispersed internal phase is 0.001-0.05 mL / min, and the flow rate of the continuous external phase is 0.01-0.5 mL / min; the components of the receiving phase are the same as those of the continuous external phase and are added with 8%-20% volume fraction of ammonia water, and the receiving phase maintains a rotation speed of 30-70 rpm at 20°C-25°C.

[0052] S3. Wash the mesoporous bioactive glass microspheres obtained in step S2 alternately with anhydrous ethanol and petroleum ether, and dry and calcine them to remove the surfactant; wherein the heating rate of the calcination treatment is 1-5°C / min, the calcination insulation temperature is 500-650°C, and the insulation time is 4-6h.

[0053] S4, dissolving the anti-tumor drug and loading it into the mesoporous channels of the mesoporous bioactive glass microspheres obtained in step S4 after removing the surfactant by an impregnation method.

[0054] (I) A mesoporous bioactive glass microsphere and its microfluidic preparation method

[0055] Example 1

[0056] (1) 4 g of P123 was fully dissolved in 60 g of ethanol, and then 0.73 g of TEP, 1.4 g of Ca(NO3)2·4H2O, 6.7 g of TEOS and 0.5 M of 1.0 g of HCl were added. After the mixture was fully dissolved, it was stirred at room temperature for 24 h and aged to obtain a mesoporous bioactive glass precursor solution.

[0057] (2) Preparation of microspheres by microfluidic device: The mesoporous bioglass precursor solution was used as the inner phase, dimethyl silicone oil was used as the outer phase, the flow rate of the outer phase was set to 0.03 mL / min, the flow rate of the inner phase was set to 0.002 mL / min, and a mixed solution of 20 mL of dimethyl silicone oil and 2 mL of ammonia water was used as the receiving phase. The microspheres were prepared by crosslinking in the receiving phase which was continuously stirred at a speed of 50 rpm.

[0058] (3) After collecting the microspheres, use anhydrous ethanol and petroleum ether to alternately wash away the residual dimethyl silicone oil on the surface of the microspheres. After cleaning, place them in a vent to dry at room temperature.

[0059] (4) Finally, the obtained dried microspheres of different sizes were placed in a muffle furnace and heated to 650°C at a rate of 1°C / min and kept at this temperature for 6 h to remove the directing agent P123. After cooling in the furnace, the mesoporous bioactive glass microspheres were obtained.

[0060] Example 2

[0061] The flow rate of the external phase was set to 0.03 mL / min, the flow rate of the internal phase was set to 0.004 mL / min, and the rest was the same as in Example 1.

[0062] Example 3

[0063] The flow rate of the external phase was set to 0.03 mL / min, the flow rate of the internal phase was set to 0.008 mL / min, and the rest was the same as in Example 1.

[0064] Example 4

[0065] The flow rate of the external phase was set to 0.06 mL / min, the flow rate of the internal phase was set to 0.002 mL / min, and the rest was the same as in Example 1.

[0066] Example 5

[0067] The flow rate of the external phase was set to 0.06 mL / min, the flow rate of the internal phase was set to 0.004 mL / min, and the rest was the same as in Example 1.

[0068] Example 6

[0069] The flow rate of the external phase was set to 0.06 mL / min, the flow rate of the internal phase was set to 0.008 mL / min, and the rest was the same as in Example 1.

[0070] Example 7

[0071] The flow rate of the external phase was set to 0.12 mL / min, the flow rate of the internal phase was set to 0.002 mL / min, and the rest was the same as in Example 1.

[0072] Example 8

[0073] The flow rate of the external phase was set to 0.12 mL / min, the flow rate of the internal phase was set to 0.004 mL / min, and the rest was the same as in Example 1.

[0074] Example 9

[0075] The flow rate of the external phase was set to 0.12 mL / min, the flow rate of the internal phase was set to 0.008 mL / min, and the rest was the same as in Example 1.

[0076] 1. Effect of different internal and external phase flow rates on the size of microspheres: The size of the mesoporous bioactive glass microspheres prepared in Examples 1 to 9 was analyzed, and the field emission scanning electron microscope observation photos and particle size distribution diagrams are shown in FIG. Figures 1-2 As shown, it is found that the diameter of the prepared microspheres is between 150μm and 450μm. When the internal phase flow rate is constant, the size of the microspheres decreases with the increase of the external phase flow rate; and when the external phase flow rate is constant, the size of the microspheres decreases with the decrease of the internal phase flow rate. At the same time, it can be found that the microspheres prepared by microfluidics are monodisperse and have uniform particle size.

[0077] 2. The influence of different internal and external phase flow rates on the microsphere pore structure: Figure 3 The transmission electron microscope observation photograph of the mesoporous bioactive glass microspheres prepared in Example 1 shows that the microspheres have a mesoporous structure. The pore structure of the mesoporous bioactive glass microspheres prepared in Examples 1 to 9 was further analyzed using a specific surface area analyzer. The results are as follows: Figure 4As shown, it was found that the specific surface area of ​​the prepared microspheres was 300-415 m 2 / g, and the average pore size is between 7nm-10nm. When the external phase flow rate is constant, as the internal phase flow rate decreases, the average pore size decreases, while the pore volume changes slightly. When the internal phase is constant, the average pore size and pore volume of the first six groups of microspheres increase with the increase of the external phase flow rate. When the internal phase is 0.002mL / min, the pore size does not change significantly with the increase of the external phase. This is because the influence of the external phase flow rate on the pore size has reached its limit and the pore size cannot be further increased.

[0078] (II) A mesoporous bioactive glass-loaded epirubicin microsphere and its microfluidic preparation method

[0079] Under light-shielding conditions, 6 mg of epirubicin was dissolved in a phosphate buffer solution (2 mg / mL) for later use, and then 200 mg of the mesoporous bioactive glass microspheres prepared in Examples 1 to 9 were added to the above solution. After oscillation at 120 rpm for 24 h in a shaking incubator, the supernatant was removed by centrifugation at 3000 rpm for 25 min, and then placed in a 37°C drying oven for drying. After complete drying, mesoporous bioactive glass microspheres loaded with epirubicin were obtained.

[0080] The drug loading results of the mesoporous bioactive glass microspheres loaded with epirubicin prepared in Examples 1 to 9 were analyzed, and it was found that the encapsulation efficiency was between 72.05% and 92.61%, and the drug loading of the mesoporous bioactive glass microspheres was 2.12% to 2.70%.

[0081] Table 1 Parameters of mesoporous bioactive glass microspheres prepared in Examples 1 to 9

[0082]

[0083] The above 9 groups of mesoporous bioactive glass microspheres loaded with epirubicin were immersed in PBS buffers with different pH values ​​(7.4, 6.2, 5.0) at a certain mass-to-volume ratio (3 mg / mL) and placed in an oscillating incubator at 37°C. The supernatant was taken out at different time points, and the corresponding absorbance was measured using a UV-visible spectrophotometer to determine the drug release capacity. At the same time, the same volume of PBS buffer was immediately added to the release system. Finally, the cumulative concentration of the drug released from the mesoporous bioactive glass microspheres loaded with epirubicin was calculated based on the following formula:

[0084]

[0085] Among them C tcorr is the corrected cumulative concentration of epirubicin at time t, C tis the apparent concentration at time t, v is the volume of the solution sample removed, and V is the total volume of the release medium.

[0086] The results are as follows Figure 5 As shown in the figure, it can be seen that each group of microspheres exhibits sustained release characteristics. Among them, under the condition of pH = 7.4, the cumulative release of microsphere drugs is much greater than the release under the conditions of pH 6.2 and 5.0. The reason is that the solubility of epirubicin increases under neutral or near-neutral pH conditions. Secondly, under neutral conditions, water molecules exist in molecular form, and hydrogen bonds are relatively weak, which is more conducive to the hydration and dissociation of epirubicin drug molecules, thereby promoting release.

[0087] (III) A mesoporous bioactive glass-loaded irinotecan microsphere and its microfluidic preparation method

[0088] 1 mg of irinotecan was dissolved in phosphate buffered saline (0.01 mg / mL) at pH=7.4 at room temperature, and 200 mg of the mesoporous bioactive glass microspheres prepared in Example 3 were added to the irinotecan-phosphate buffer solution. After shaking at 120 rpm in a shaking incubator for 24 h, the supernatant was collected by centrifugation at 3000 rpm for 25 min, and then placed in a freeze dryer for drying. After complete drying, mesoporous bioactive glass microspheres loaded with irinotecan were obtained.

[0089] Analysis of the drug loading results showed that the irinotecan encapsulation efficiency was 67.2% and the drug loading amount was 1.63%.

[0090] (IV) A mesoporous bioactive glass-loaded catalase microsphere and its microfluidic preparation method

[0091] Under light-shielding conditions, 10 mg of catalase was dissolved in a phosphate buffer solution (2 mg / mL) at pH = 7.4, and 250 mg of the mesoporous bioactive glass microspheres prepared in Example 3 were added to the catalase-phosphate buffer solution. After oscillation at 120 rpm for 24 h in a shaking incubator, centrifugation at 3000 rpm for 25 min was performed, and then the microspheres were placed in a freeze dryer for drying. After complete drying, mesoporous bioactive glass microspheres loaded with catalase were obtained.

[0092] Analysis of the drug loading results showed that the peroxidase encapsulation efficiency was 69.16% and the drug loading was 2.66%.

[0093] The above description of the embodiments is to facilitate the understanding and use of the invention by those skilled in the art. It is obvious that those skilled in the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative work. Therefore, the present invention is not limited to the above embodiments, and improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the present invention should be within the scope of protection of the present invention.

Claims

1. A mesoporous bioactive glass drug-loaded microsphere preparation, characterized in that: The microsphere preparation uses mesoporous bioactive glass microspheres as a skeleton, on which anti-tumor drugs are loaded.

2. The mesoporous bioactive glass drug-loaded microsphere preparation according to claim 1, characterized in that: The particle size of the mesoporous bioactive glass microspheres is 150-45 μm; the mesoporous bioactive glass microspheres have a mesoporous structure, the mesopore diameter is 5-12 nm, and the specific surface area of ​​the mesoporous bioactive glass microspheres is 300-500 m 2 / g; the anti-tumor drug is loaded in the mesoporous channels of the mesoporous bioactive glass microspheres, the drug loading rate of the mesoporous bioactive glass microspheres is 2.12% to 2.70%, and the encapsulation rate is 72.05% to 92.61%.

3. The mesoporous bioactive glass drug-loaded microsphere preparation according to claim 1, characterized in that: The mesoporous bioactive glass microspheres include SiO2-P2O5 binary oxide or SiO2-CaO-P2O5 ternary oxide.

4. The mesoporous bioactive glass drug-loaded microsphere preparation according to claim 3, characterized in that: When the mesoporous bioactive glass microspheres are SiO2-P2O5 binary oxides, the molar ratio of SiO2 to P2O5 is (70-90):(10-30); when the mesoporous bioactive glass microspheres are SiO2-CaO-P2O5 ternary oxides, the molar ratio of SiO2, CaO and P2O5 is (70-90):(5-15):(5-15).

5. The mesoporous bioactive glass drug-loaded microsphere preparation according to claim 1, characterized in that: The anti-tumor drug comprises one or more combinations of epirubicin, idarubicin, oxaliplatin, irinotecan, topotecan, sorafenib and catalase.

6. A method for preparing a mesoporous bioactive glass drug-loaded microsphere preparation as claimed in any one of claims 1 to 5, characterized in that: The method comprises the following preparation steps: S1, weighing silicon, calcium, and phosphorus precursor compounds according to the molar ratio of each element in the mesoporous bioactive glass microspheres, using a nonionic surfactant as a structure directing agent, performing a sol-gel reaction under acidic conditions, and then obtaining a mesoporous bioactive glass precursor solution through an aging treatment; S2. Using a microfluidic method, the mesoporous bioactive glass precursor solution obtained in step S1 is used as a dispersed internal phase and the oil phase is used as a continuous external phase to obtain monodisperse droplets, and the droplets are cross-linked in a receiving phase to prepare mesoporous bioactive glass microspheres; S3, washing, drying, and calcining the mesoporous bioactive glass microspheres obtained in step S2 to remove the surfactant; S4. Loading the anti-tumor drug into the mesoporous channels of the mesoporous bioactive glass microspheres obtained in step S4 after removing the surfactant by an impregnation method.

7. The method for preparing a mesoporous bioactive glass drug-loaded microsphere preparation according to claim 6, characterized in that: In step S1, the silicon precursor compound is selected from one or more of tetramethylsilane and tetraethylsilane, the calcium precursor compound is selected from one or more of calcium nitrate and calcium chloride, and the phosphorus precursor compound is selected from triethyl phosphate; the nonionic surfactant is selected from any one of the triblock copolymers P123, P108, F127, and F108; the sol-gel reaction time is 12 to 48 hours, and the aging time is 3 to 7 days.

8. The method for preparing a mesoporous bioactive glass drug-loaded microsphere preparation according to claim 6, characterized in that: In step S2, the oil phase is selected from any one of liquid paraffin, mineral oil, dimethyl silicone oil, and n-heptane; the flow rate of the dispersed internal phase is 0.001-0.05 mL / min, and the flow rate of the continuous external phase is 0.01-0.5 mL / min; the component of the receiving phase is the same as that of the continuous external phase and is added with 8%-20% volume fraction of ammonia water, and the receiving phase maintains a rotation speed of 30-70 rpm at 20°C-25°C.

9. The method for preparing a mesoporous bioactive glass drug-loaded microsphere preparation according to claim 6, characterized in that: In step S3, the heating rate of the calcination treatment is 1-5°C / min, the calcination insulation temperature is 500-650°C, and the insulation time is 4-6h.

10. Use of the mesoporous bioactive glass drug-loaded microsphere preparation according to any one of claims 1 to 5 in preparing drugs for tumor embolization therapy.

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