Multi-connected microsphere coated drug carrier, preparation method and application thereof

Abstract

This invention discloses a multi-microsphere-coated drug carrier, its preparation method, and its application. The drug carrier uses drug-loaded attapulgite particles as a core, with the core surface coated by interconnected PLGA microspheres. The surface of the drug carrier is uneven and porous. The preparation method of the drug carrier involves: obtaining attapulgite particles through spray granulation, loading the drug into the attapulgite particles, and then coating the attapulgite particles with PLGA. The drug carrier provided by this invention exhibits good sustained-release performance and safety, and is of great significance for antitumor drug delivery.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to a drug carrier that improves drug release rate by combining nano-inorganic materials with polymer materials, as well as the preparation method of the drug carrier and its application in the preparation of anti-tumor drugs. Background Technology

[0002] Cancer is the biggest killer of human life and health and one of the major challenges facing the medical community today. Chemotherapy is the most important means of cancer treatment, but traditional chemotherapy has disadvantages such as large toxic side effects, low drug bioavailability, and serious drug burst release problems, which limit its application and development in cancer treatment. Moreover, most chemotherapy drugs lack the ability to reach tumor tissue and lack selective killing effect on tumor cells. While killing tumor cells, they also damage normal cells. In particular, cancer cells develop drug resistance due to drug administration. In order to overcome the drug resistance of cancer cells, higher doses of anticancer drugs are required, which causes greater side effects on normal cells and may even interrupt treatment. On the other hand, the efficacy of most antitumor drugs is also limited by their own properties, such as poor water solubility and narrow therapeutic window.

[0003] Since the 1970s, drug carriers have attracted considerable attention as chemotherapeutic drug delivery systems for cancer treatment. The particles used in drug delivery systems range in size from 10 to 1000 nm and can be composed of various materials, including polymers, lipids, viruses, and organometallic complexes. With further research, this field has gradually expanded to include dendritic macromolecules, micelles, polymer nanospheres, and inorganic nanomaterials (such as gold, silicon, metals, and iron oxide). Nanotechnology-based drug delivery is one of the emerging fields in cancer treatment.

[0004] Currently, although various materials are at a very advanced stage, exploration in this field is far from sufficient, especially in terms of breakthroughs in preparation methods and drug carrier structures. Traditional emulsification solvent evaporation technology, spray drying technology, and layer-by-layer self-assembly technology are commonly used methods for preparing drug carriers. Whether these methods can be innovated independently or in combination to create novel preparation methods remains to be solved. Furthermore, due to the significant differences in the physiological environment of different parts of the human body, and the need for customized treatment methods for different diseases and drugs, different scenarios often require different approaches. Utilizing nanomaterials as carriers for anti-tumor drugs to construct novel intelligent response systems can achieve sustained drug release and stabilize drug concentrations in the blood, thereby reducing toxic side effects on patients and improving the therapeutic effect of tumors, which is also a current research hotspot. Summary of the Invention

[0005] In view of this, the present invention utilizes nano-inorganic materials and polymer materials to construct a novel drug carrier, which can improve the encapsulation efficiency of water-soluble drugs, improve the problem of drug burst release, and effectively solve the embolism caused by large-size drug carriers.

[0006] The specific technical solution of the present invention is as follows:

[0007] The first aspect of the present invention provides a drug carrier coated with multiple microspheres, wherein the drug carrier has attapulgite particles loaded with drugs as the core and the surface of the core is coated with interconnected PLGA microspheres, and the surface of the drug carrier is uneven and porous.

[0008] This invention utilizes the strong adsorption capacity of attapulgite (ATT) for drug molecules to achieve drug loading, and then coats the drug-loaded attapulgite particles, which helps to improve the drug encapsulation efficiency. Furthermore, during coating, the nanoscale effect of attapulgite is utilized to form a unique multi-microsphere structure, making the drug carrier surface both porous and uneven. This facilitates drug release and carrier degradation, effectively avoiding the embolism problem caused by carriers prepared by traditional emulsion solvent evaporation methods, which are often due to their large particle size and slow PLGA degradation rate, leading to entry into blood vessels in human tissues. In addition, this invention combines the granulation of attapulgite inorganic nanomaterials with polylactic-co-glycolic acid copolymer (PLGA), a polymer with good biocompatibility, to form a drug carrier with fewer side effects on the human body, effectively delivering the drug while minimizing toxic side effects.

[0009] Preferably, in the above-mentioned drug carrier, the attapulgite particles are spherical with a size of 15-30 μm, and the PLGA microspheres have a size of 200-500 nm.

[0010] More preferably, in the above-mentioned drug carrier, the overall size of the drug carrier is between 30-50 μm.

[0011] Preferably, the drug in the above-mentioned drug carrier can be a water-soluble drug. Currently, most drug carriers prepared by existing technologies have poor encapsulation effects on water-soluble drugs that are sensitive to temperature and light, or suffer from material inactivation due to high temperatures, or experience significant drug loss due to preparation in aqueous solutions. The novel drug carrier provided by this invention can effectively improve the problem of low encapsulation efficiency for water-soluble drugs; for example, when the water-soluble drug is doxorubicin hydrochloride (DOX), its overall encapsulation efficiency can reach over 95%.

[0012] In one embodiment of the present invention, the water-soluble drug is doxorubicin hydrochloride, and the resulting drug carrier is macroscopically a red granular substance that must be stored in the dark at a low temperature of 2-8°C. Due to the excellent water absorption properties of attapulgite, doxorubicin hydrochloride mainly exists in the attapulgite particles in the form of pore adsorption. Furthermore, doxorubicin hydrochloride is acidic when dissolved in water, while the OH- ions in attapulgite... - This gives it a certain ability to bind.

[0013] A second aspect of the present invention provides a method for preparing the above-mentioned multi-microsphere-coated drug carrier, specifically comprising the following steps:

[0014] S1. After mixing the slurry containing attapulgite, binder and dispersant, spray granulation is performed to obtain attapulgite particles.

[0015] S2. Load the drug into the attapulgite particles;

[0016] S3. The attapulgite particles loaded with drug obtained in step S2 are coated with PLGA to improve their drug release rate.

[0017] Preferably, in the above method, the slurry in step S1 contains: 20-30 wt% attapulgite, 1.5-3.0 wt% dispersant, and 0.2-1.0 wt% binder. In one embodiment of the present invention, the slurry is composed of attapulgite, ammonium polyacrylate (dispersant), polyvinyl alcohol (binder), and deionized water.

[0018] Preferably, in the above method, the attapulgite is subjected to calcination pretreatment before being prepared into a slurry to remove impurities, surface adsorbed water, and pore water, thereby improving the drug loading capacity of the attapulgite. More preferably, the heating method for the calcination pretreatment is: slow heating with the final temperature controlled above 200°C and not exceeding 450°C, and held for more than 10 hours.

[0019] Preferably, in the above method, the slurry can be mixed by ball milling.

[0020] In the above method, the feed rate and temperature during spray granulation are key factors affecting the shape and size of attapulgite particles. Therefore, the feed rate should not be too fast during spray granulation, such as maintaining it at around 12 mL / min, and the temperature during the process should be controlled above 120℃.

[0021] Preferably, in the above method, after the spray granulation forms uniform attapulgite particles with the required size, the attapulgite particles are degreased to remove dispersants that are harmful to the human body and to solidify the particles.

[0022] More preferably, the attapulgite particles are deesterified at a temperature not exceeding 420°C, and the heating method is slow heating.

[0023] In the above method, different methods can be selected to load the drug onto the attapulgite particles according to the different properties of the drug. For example, in one embodiment of the present invention, the drug is the water-soluble drug doxorubicin hydrochloride, and the loading is carried out in the following way: the attapulgite particles are suspended in an aqueous solution and stirred, the doxorubicin hydrochloride solution is mixed with it, and the mixture is protected from light while being stirred at a constant speed of 200-500 r / min for 24 hours to complete the drug loading; then the suspension of doxorubicin hydrochloride-loaded attapulgite is directly poured into a petri dish and placed in a -40°C freezer until completely frozen and no liquid exists, then covered with plastic wrap and punctured for freeze-drying to obtain dried attapulgite particles loaded with doxorubicin hydrochloride.

[0024] Preferably, in the above method, when the drug is doxorubicin hydrochloride, the mass ratio of the attapulgite particles to the doxorubicin hydrochloride should not exceed 4:1.

[0025] Preferably, in the above method, step S3 specifically involves: dispersing the drug-loaded attapulgite particles obtained in step S2 in a solvent containing dissolved PLGA, adding PVA solution, emulsifying, and then adding PBS solution. After the solvent has completely evaporated and the drug-loaded particles have solidified, the particles are centrifuged, washed, and freeze-dried to obtain the drug carrier.

[0026] In the above method, the present invention utilizes the nano-size effect of attapulgite. During the coating stage, when PLGA is solidified into spheres, the nanoneedle-like material on the surface of attapulgite particles (DOX-ATT-MS) loaded with doxorubicin hydrochloride after spray granulation is used as the core, and a large number of nanospheres are deposited on the surface on their own. Furthermore, by controlling the feed ratio of PLGA and DOX-ATT-MS, a drug carrier structure with an uneven and porous surface can be formed by interconnecting PLGA microspheres with a size of 200-500 nm.

[0027] More preferably, the PLGA is ester-terminated PLGA with a molecular weight of 3-5w. During the experiments of this invention, it was found that different PLGA molecular weights affect their binding ability to the surface of attapulgite particles. When the molecular weight is between 3w and 5w, the resulting drug carrier has a better effect. The coating effect also varies significantly when different types of PLGA are used; for example, using carboxyl-terminated PLGA often results in PLGA forming individual spheres, failing to achieve a good coating effect.

[0028] More preferably, the mass ratio of PLGA to the drug-loaded attapulgite particles in step S3 is 3:2.

[0029] More preferably, the solvent in step S3 is a volatile organic solvent, including but not limited to dichloromethane, tetrahydrofuran, etc. It can be understood that the purpose of using the solvent in this step includes to achieve emulsification, dissolve PLGA, and gradually evaporate during the subsequent processing to achieve PLGA deposition, etc. Therefore, in principle, any solvent that meets the above purpose can be used.

[0030] More preferably, the concentration of the PVA solution in step S3 is 2 wt%; during the emulsification process, the optimal volume ratio of the solvent to the 2 wt% PVA solution is 1:2.

[0031] More preferably, the centrifugal washing conditions in step S3 are 7000-8500 rpm for 3-10 min to fully remove PVA adhering to the surface of the drug carrier.

[0032] The third aspect of this invention provides the application of the above-mentioned multi-microsphere-coated drug carrier in the preparation of drugs.

[0033] In one embodiment of the present invention, the drug carrier is loaded with the antitumor drug doxorubicin hydrochloride, and experimental data show that the drug carrier loaded with doxorubicin hydrochloride has a better in vitro anticancer effect at the same actual drug concentration. It can be seen that the drug carrier has important significance in the field of drug preparation.

[0034] The beneficial effects of this invention are as follows:

[0035] (1) This invention creatively utilizes the nano-size effect of attapulgite to coat its surface with a protective layer formed by countless nano-sized PLGA microspheres. This achieves effective sustained drug release while accelerating the deconstruction of the drug carrier itself, effectively reducing the possibility of embolism in large-sized drug-loaded microspheres.

[0036] (2) Compared with the problem that the drug release rate is too fast due to the nano-size of attapulgite when the drug is loaded directly, the present invention creatively performs spray granulation to make it agglomerate into particles, and then loads the drug onto them. This not only effectively avoids drug inactivation caused by high temperature, but also the particles gradually decompose during the sustained release process, reducing the burst release of the drug and enhancing the sustained release ability.

[0037] (3) In this invention, after loading the drug with attapulgite particles with strong adsorption capacity, the drug-loaded attapulgite particles are then coated with PLGA, which greatly improves the problem of low drug (especially water-soluble drugs) encapsulation rate, and the overall encapsulation rate can reach more than 95%.

[0038] (4) This invention combines granulation of inorganic nanomaterials such as attapulgite with PLGA, a polymer material with good biocompatibility, to form a drug sustained-release system with fewer side effects on the human body, thereby killing tumors while reducing toxic side effects on the human body. Attached Figure Description

[0039] Figure 1 The infrared spectrum of the DOX-ATT-PLGA-MS prepared according to this invention.

[0040] Figure 2 The image shows the XRD pattern of the DOX-ATT-PLGA-MS prepared according to this invention.

[0041] Figure 3 SEM comparison images of DOX-ATT-PLGA-MS prepared for this invention before and after PLGA surface coating.

[0042] Figure 4 The cumulative release curve of DOX-ATT-PLGA-MS prepared for this invention in vitro.

[0043] Figure 5 The in vitro drug burst release curve of DOX-ATT-PLGA-MS prepared for this invention.

[0044] Figure 6 The image shows the results of the anticancer activity detection of the DOX-ATT-PLGA-MS prepared in this invention. Detailed Implementation

[0045] To better understand the present invention, the following detailed description, in conjunction with specific embodiments and accompanying drawings, further clarifies the content of the invention. It should be understood that the specific embodiments described herein are for illustrative and explanatory purposes only and are not intended to limit the scope of the invention.

[0046] Unless otherwise specified, the methods described in the following examples are conventional; the reagents and materials described are commercially available unless otherwise specified.

[0047] Example 1

[0048] Taking doxorubicin hydrochloride as an example, this example demonstrates the preparation of a multi-microsphere-coated antitumor sustained-release drug carrier, the preparation process of which is as follows:

[0049] (1) Pretreatment of original attapulgite soil.

[0050] 20g of raw attapulgite was weighed and calcined in a muffle furnace, with the temperature increasing by 5°C every 10 minutes until it reached 220°C, and then maintained at 220°C for 24 hours. TG-DSC analysis showed that this heating regime successfully removed surface water, grease, and most of the pore water.

[0051] (2) Prepare slurry and spray granulation.

[0052] 200 mL of deionized water, 7 g of 10% polyvinyl alcohol, 4.5 g of ammonium polyacrylate, and 70 g of attapulgite were added to a ball mill jar. After preparation, the mixture was ball-milled for 24 h. Attapulgite particles were prepared using a HOLVES SPARY DRYER with a feed rate of 12 mL / min and a drying temperature of 150 °C. Electron microscopy (SEM) observation showed that the prepared attapulgite particles had a size between 15 and 30 μm, and all particles were spherical and relatively uniform in shape.

[0053] (3) Deesterification treatment.

[0054] The dispersant in the attapulgite particles prepared in step (2) was removed and solidified using a deesterification furnace. The temperature was increased by 5°C every 10 minutes until it reached 330°C. Infrared spectral analysis showed that the dispersant ammonium polyacrylate was removed.

[0055] (4) Drug load.

[0056] 175 mg of attapulgite particles were dispersed in 10 mL of deionized water and kept for 5 min. Simultaneously, 35 mg of doxorubicin hydrochloride was completely dissolved in 10 mL of deionized water. The dissolved doxorubicin hydrochloride solution was then added to the attapulgite particle dispersion. The mixture was protected from light and stirred at a constant speed of 200-300 rpm for 24 h to complete drug loading. The suspension of doxorubicin hydrochloride-loaded attapulgite was poured directly into a petri dish and pre-cooled at -40°C for 1 h. Then, it was covered with plastic wrap, punctured, and freeze-dried to obtain dried attapulgite particles loaded with doxorubicin hydrochloride.

[0057] The supernatant obtained by centrifugation of partially loaded doxorubicin hydrochloride granules was subjected to ultraviolet spectrophotometric analysis, which showed that the drug encapsulation rate was 96%, indicating a good loading effect.

[0058] (5) Multi-microsphere coating process.

[0059] Surface coating was performed using 4.5W molecular weight, 85:15 ester-terminated PLGA. First, 50mg of doxorubicin hydrochloride-loaded attapulgite particles prepared in the previous step were dispersed in 5mL of dichloromethane solution containing 75mg of PLGA dissolved in advance. Then, 10mL of 2% PVA solution (volume ratio 2:1) was dissolved in the PLGA and the mixture was thoroughly emulsified in an ultrasonic emulsifier. The specific ultrasonic emulsifier settings were: 3 seconds of sonication, 2 seconds of pause, for a total of 3 minutes, 40% power, with ice-water bath treatment (3, 2, 3 min, 40%).

[0060] The mixture was then added to 60 mL of pre-prepared PBS solution. The mixture was first stirred at high speed for 1 min, followed by uniform and slow stirring for 10 h to allow the dichloromethane to completely evaporate and the drug carrier to solidify. After preparation, the PVA adhering to the surface was thoroughly washed off in a centrifuge at 7000 rpm for 5 min. This process was repeated 5 times. The mixture was then removed and placed in a disposable petri dish for pre-cooling at -40°C for 1 h. After that, it was covered with plastic wrap and punctured for freeze-drying to obtain a dried multi-microsphere-encapsulated novel antitumor sustained-release drug carrier, denoted as DOX-ATT-PLGA-MS.

[0061] Comparative Example 1

[0062] Unlike Example 1, this example does not include step (5), but is otherwise the same as Example 1.

[0063] Comparative Example 2

[0064] In this example, the attapulgite is not spray-granulated, that is, the attapulgite loaded with doxorubicin hydrochloride is prepared according to steps (1) and (4) in Example 1 without spray granulation.

[0065] The drug carrier synthesized in Example 1 was subjected to the following tests:

[0066] 1. Infrared detection.

[0067] To demonstrate that the model drug (i.e., doxorubicin hydrochloride) was successfully loaded into the drug delivery system of the present invention and that PLGA was coated on the surface, the chemical composition was verified by comparing the Fourier transform infrared (FTIR) spectra of the bare drug doxorubicin hydrochloride (DOX), 85:15 ester-terminated PLGA, attapulgite (ATT), and DOX-ATT-PLGA-MS.

[0068] Infrared detection results as follows Figure 1 As shown, from top to bottom, the infrared spectrum of attapulgite, the infrared spectrum of PLGA (85:15), the infrared spectrum of doxorubicin hydrochloride, and the infrared spectrum of DOX-ATT-PLGA-MS are shown.

[0069] Analysis shows that it is 1190cm -1 The typical absorption peak at 1414 cm⁻¹ is attributed to the stretching vibration of CN loaded with DOX. -1 The peak may be attributed to the in-plane tensile vibration of the DOX C single-bond skeleton at 3527 cm⁻¹. -1 and 3326 cm -1 This is due to the bending vibration of NH. The PLGA macromolecule has four main infrared absorption peaks, with the peak at 2947 cm⁻¹. -1 and 2997cm -1 The peak at 1752 cm⁻¹ is a vibrational peak caused by carbon-hydrogen bonds.-1 It is caused by the vibration of the carbonyl ketone group, 1456 cm -1 The location is caused by the methylene stretching vibration peak. For attapulgite, 3546 cm⁻¹ -1 and 343cm -1 The absorption peak at 1654 cm⁻¹ corresponds to the OH stretching vibration of water in ATT. -1 The absorption zone at 985cm is formed by the bending vibrations of the absorbed water in the channel. -1 The absorption band is a fingerprint of fibrous clay minerals. It is visible at 1188 cm⁻¹ on the DOX-ATT-PLGA-MS infrared spectrum. -1 The CN stretching vibration peak at 2947 cm⁻¹ indicates that DOX was successfully loaded into the drug delivery system. -1 and 2997cm -1 A very obvious PLGA carbon-hydrogen bond vibration peak can be seen at this point, and there is also a peak at 985 cm⁻¹. -1 The fingerprint characteristic peaks can be used to prove from the chemical composition that several materials are present in the drug delivery system.

[0070] 2. XRD analysis.

[0071] XRD test results are as follows Figure 2 As shown, from top to bottom, the XRD patterns are: attapulgite (ATT), PLGA (85:15), doxorubicin hydrochloride (DOX), and DOX-ATT-PLGA-MS.

[0072] As shown in the figure, the DOX-ATT-PLGA-MS surface did not exhibit obvious diffraction peaks for doxorubicin hydrochloride, but only showed relatively weak diffraction peaks for attapulgite. This indicates that the attapulgite particles loaded with doxorubicin hydrochloride were indeed successfully encapsulated within the drug carrier by PLGA nanospheres.

[0073] 3. SEM detection.

[0074] SEM detection results are as follows: Figure 3 As shown, A is a SEM image of DOX-ATT-PLGA-MS, and B is a SEM image of attapulgite particles loaded with doxorubicin hydrochloride without PLGA coating (DOX-ATT-MS).

[0075] from Figure 3 It can be seen that after loading doxorubicin hydrochloride onto attapulgite, its nano-size effect is utilized to coat PLGA with a layer of nano-sized multi-microsphere structure, thus realizing the uneven and porous surface state of DOX-ATT-PLGA-MS.

[0076] 4. Drug sustained-release and burst-release testing.

[0077] The drug carriers loaded with doxorubicin hydrochloride prepared in Example 1 and Comparative Examples 1-2 were subjected to drug release assays in PBS buffer solution at pH 5.5, and in vitro cumulative release curves were plotted.

[0078] The drug carriers loaded with doxorubicin hydrochloride prepared in Example 1 and Comparative Examples 1-2 were subjected to drug burst release detection in PBS buffer solution at pH 5.5, and drug burst release curves were plotted.

[0079] Test results as follows Figure 4 and Figure 5 As shown, the release rate of doxorubicin hydrochloride-loaded attapulgite clay without microsphere coating was significantly faster than that of the drug carrier with microsphere coating, regardless of whether spray granulation was performed. This indicates that the drug carrier has certain performance improvements in both sustained-release and burst-release of drugs.

[0080] 5. Anticancer activity detection.

[0081] The following methods were used for detection: blank microspheres (prepared according to steps (1) to (3) of Example 1), bare drug, uncoated carrier group (prepared in Comparative Example 1), and multi-microsphere coated group (i.e., DOX-ATT-PLGA-MS) were set up to determine antitumor activity. Six parallel control groups were set up for each group. The materials were irradiated with ultraviolet light in a clean bench for half a day. After culturing the cells for 24 hours, the culture medium was removed, and uncoated drug carrier and multi-microsphere coated (0.01-100 μg / mL, 20 μL complete culture medium) with concentrations equivalent to the bare drug doxorubicin hydrochloride were added to the culture medium at a cell density of 5×10⁶ cells / mL. 3 Cells were placed in 96-well plates. After 48 hours, CCK-8 solution (10 μL, 2 h) was added and incubated. Cell viability was determined by measuring the absorbance at 450 nm using a microplate reader. The results are as follows: Figure 6 As shown in Figure A.

[0082] In addition, the same method was used to determine the cell viability of MG63 human osteosarcoma cells after incubation with uncoated drug carriers and multi-microspheres at equivalent doxorubicin hydrochloride concentrations (0.01-100 μg / mL) for 24, 48, and 72 hours to compare their antitumor effects. The results are as follows: Figure 6 As shown in B.

[0083] The test results above show that DOX-ATT-PLGA-MS has a better in vitro anticancer effect at the same actual drug concentration.

[0084] The upper and lower limits and ranges of the substances listed in this invention, as well as the upper and lower limits and ranges of the process parameters, can all realize this invention, and will not be listed one by one here.

[0085] In summary, this invention combines spray drying technology and emulsified solvent evaporation technology with the nanoscale effect of attapulgite to prepare a drug carrier with good sustained-release performance. Furthermore, the drug carrier has a certain porosity and an uneven structure, which is beneficial for drug release and carrier degradation, thereby reducing the possibility of embolization of large-sized drug-loaded microspheres. This drug carrier also improves the problem of poor encapsulation efficiency caused by the preparation of water-soluble drugs, such as doxorubicin hydrochloride, in aqueous solutions. Therefore, this drug carrier has broad application prospects.

[0086] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any changes or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in the present invention should be included within the scope of protection of the present invention.

Claims

1. A drug carrier coated with multi-microspheres, characterized in that, The drug carrier has an attapulgite particle loaded with doxorubicin hydrochloride as its core, and the surface of the core is covered with interconnected PLGA microspheres. The surface of the drug carrier is uneven and porous. The attapulgite particles are spherical with a size of 15-30 μm, the PLGA microspheres have a size of 200-500 nm, and the drug carrier has a size of 30-50 μm. The method for preparing the drug carrier includes the following steps: S1. After mixing the slurry containing 20-30wt% attapulgite, 0.2-1.0wt% binder and 1.5-3.0wt% dispersant, spray granulation is performed to obtain attapulgite particles. S2. Load the drug into the attapulgite particles; S3. Disperse the drug-loaded attapulgite particles in a solvent containing PLGA, add PVA, emulsify, and then add to PBS solution. After the solvent has completely evaporated and the drug-loaded particles have solidified, centrifuge, wash, and freeze-dry to obtain the drug carrier; wherein the PLGA is ester-terminated PLGA with a molecular weight of 3-5w.

2. The drug carrier according to claim 1, characterized in that, In step S2, the attapulgite particles are degreased before being loaded with drugs.

3. The use of the drug carrier as described in claim 1 in the preparation of a drug.

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