Multi-layer magnetic soft robot, and preparation method and control method therefor

Abstract

A multi-layer magnetic soft robot, and a preparation method and control method therefor. The multi-layer magnetic soft robot is of a three-layer structure, which comprises a top layer, a central layer and a bottom layer, wherein each layer comprises a magnetic flexible substrate and a medication-loaded adhesive film, and the three-layer structure is self-assembled under the action of magnetic attraction and can be curled and placed into a conventional medicinal capsule. Each layer of the structure of the robot comprises a medication-loaded adhesive film, and thus the robot can deliver medication to a plurality of targets; and due to the provision of an adhesive, the medication-loaded adhesive film can realize tissue adhesion with a target, so that medication has the capability of staying at the target for a long time, which makes the sustained and precise release of the medication possible. The magnetic flexible substrate provides a self-assembly mode for the robot, so that the robot can accurately reach a target under the action of an external magnetic field. Finally, the multi-layer medication-loaded structure of the robot makes multi-target treatment of diseases possible, and the robot is simple to operate, has a low cost, and achieves truly non-invasive treatment.

Description

A multi-layer magnetic soft robot and its preparation method and control method Technical Field

[0001] The present invention relates to the field of biomedical engineering, and in particular to a multi-layer magnetic soft robot and a preparation method and a control method thereof. Background Art

[0002] Currently, patients with mild inflammation caused by gastric ulcers typically use oral medications. However, for more serious complications of gastric ulcers, such as bleeding and perforation, doctors often resort to interventional, invasive surgical procedures. Because the lesions occur in the stomach, the largest digestive organ in the body, and its complex physiological environment, conventional medical treatments inevitably face the following challenges: First, while swallowed medications easily reach the stomach, drug molecules are less stable in an acidic environment, and gastric peristalsis makes it difficult for drugs to anchor to their target sites. Consequently, only a small amount of the drug reaches the site of inflammation, resulting in poor targeting, low efficacy, and a slow treatment process. Second, while interventional and surgical treatments are considered the fastest and most effective options for bleeding and perforation caused by gastric ulcers, they can be painful during and after the procedure, impacting patients' lives for a period of time. Third, gastric ulcers are a common and recurrent disease, and achieving multi-target treatment with a single interventional procedure is a significant challenge.

[0003] In recent years, small robots have made significant progress in biomedical applications, particularly in targeted drug delivery. With the advancement of research, control methods for small robots have also been developed. Light fields, electric fields, ultrasound, and magnetic fields can all be used to achieve navigational motion. Compared to other actuation methods, magnetic fields offer strong penetrability and good biocompatibility. Therefore, non-invasive magnetic drug-carrying robots have attracted attention and are considered the ideal next-generation carriers for targeted drug delivery. Some researchers have fabricated a series of soft magnetic robots that can grasp and release drugs by inducing deformation. Others have focused on magnetic micro- and nanorobots, including biohybrid micro- and nanorobots and cavity-based micro- and nanorobots. These robots load drugs and magnetic particles through surface modification and internalization, achieving effective targeted drug delivery under the influence of an external magnetic field and drug release at the target site under the stimulation of the external environment. Compared to oral medications, they offer a more targeted approach and provide a non-invasive and precise drug delivery method compared to surgical intervention. However, although aggregation at the target site can be achieved, the released drugs still have difficulty resisting gastric peristalsis due to their lack of target anchoring ability, resulting in low drug efficacy.

[0004] Therefore, the existing technology needs to be improved.

[0005] Summary of the Invention

[0006] In view of the above-mentioned deficiencies in the prior art, the purpose of the present invention is to provide a multi-layer magnetic soft robot and its preparation method and control method, aiming to solve the problem in the prior art that the delivery robot lacks target anchoring ability when releasing drugs, resulting in low drug efficacy.

[0007] The technical solutions of the present invention are as follows:

[0008] A multi-layer magnetic soft robot comprises a top layer, a bottom layer, and a center layer arranged between the top layer and the bottom layer. Each layer comprises a drug-loaded adhesive film and a magnetic flexible substrate. The three-layer structure self-assembles into the multi-layer magnetic soft robot under the magnetic force of the flexible substrate.

[0009] The multi-layer magnetic soft robot comprises: the flexible base of the central layer is composed of a non-magnetic frame and a magnetic bottom; the flexible base of the top layer or the bottom layer is composed of a magnetic frame and a non-magnetic bottom.

[0010] In the multi-layer magnetic soft robot, the material of the magnetic bottom or the magnetic frame contains ferromagnetic particles, and the material of the non-magnetic bottom or the non-magnetic frame contains silica gel.

[0011] In the multi-layer magnetic soft robot, the ferromagnetic particles are neodymium iron boron, and the silica gel includes one or more of polydimethylsiloxane and Ecoflex series silica gel.

[0012] In the multi-layer magnetic soft robot, the material of the drug-loaded adhesive film includes bioadhesive material and adjuvant.

[0013] In the multi-layer magnetic soft robot, the drug-loaded adhesive films of the top layer, the center layer and the bottom layer are loaded with the same drug, or are respectively loaded with different drugs.

[0014] A method for preparing a multilayer magnetic soft robot as described above, comprising the steps of:

[0015] Preparation of magnetic films, non-magnetic films and drug-loaded adhesive films;

[0016] Cutting the magnetic film into a magnetic base and a magnetic frame, and cutting the non-magnetic film into a non-magnetic base and a non-magnetic frame;

[0017] Assembling the top layer, the center layer and the bottom layer respectively, wherein the center layer is composed of a non-magnetic frame, a magnetic bottom and a drug-loaded adhesive film, and the top layer or the bottom layer is composed of a magnetic frame, a non-magnetic bottom and a drug-loaded adhesive film;

[0018] The assembled top layer, center layer and bottom layer are placed in a magnetic field for magnetization, and the three-layer structure self-assembles into the multi-layer magnetic soft robot under the action of the magnetic force.

[0019] A control method for a multi-layer magnetic soft robot as described above, comprising the steps of:

[0020] A multilayer magnetic soft robot is provided, comprising a top layer, a center layer, and a bottom layer, wherein the structure of each layer comprises a drug-loaded adhesive film and a magnetic flexible substrate;

[0021] Apply magnetic force to the robot through a permanent magnet to control it to move to target point one;

[0022] Fix the permanent magnet so that the drug-loaded adhesive film on the bottom layer of the robot adheres to the target;

[0023] Flip the permanent magnet to change the direction of the magnetic field, so that the robot can flip over and separate from the bottom layer.

[0024] Continue to maintain the direction of the permanent magnet and control the robot that has left the bottom layer to move to target point 2;

[0025] Fix the permanent magnet so that the drug-loaded adhesive film on the top layer of the robot adheres to target 2;

[0026] Flip the permanent magnet to change the direction of the magnetic field, so that the robot can flip and detach from the top layer.

[0027] Continue to maintain the direction of the permanent magnet and control the robot that has separated from the bottom and top layers to move to target point three;

[0028] The permanent magnet is fixed so that the drug-loaded adhesive film on the center layer of the robot adheres to target point three.

[0029] An application of a multi-layer magnetic soft robot, wherein the multi-layer magnetic soft robot as described above is applied to the preparation of multi-target therapeutic drugs.

[0030] The application, wherein the multi-layer magnetic soft robot is applied to the preparation of drugs for multi-target treatment of gastric inflammation or gastric ulcer.

[0031] Beneficial effects: The present invention provides a multi-layer magnetic soft robot and its preparation and control methods. The multi-layer magnetic soft robot consists of a three-layer structure, including a top layer, a center layer, and a bottom layer. Each layer contains a magnetic flexible substrate and a drug-loaded adhesive film. The three-layer structure achieves self-assembly under the action of magnetic attraction and can be curled up and placed into a conventional pharmaceutical capsule. Each layer of the robot structure contains a drug-loaded adhesive film, which can deliver drugs to multiple targets, providing the possibility of multi-target treatment; and due to the presence of the adhesive, it can achieve tissue adhesion with the target, so that the drug has the ability to remain in the target for a long time, providing the possibility of continuous and precise release of the drug, and achieving long-term treatment. The magnetic flexible substrate provides a way for the robot to self-assemble, and its bonding strength is sufficient to achieve the robot's translational and tumbling motion, so that the robot can accurately reach the target position in different motion modes under the action of an external magnetic field. Ultimately, the multi-layer drug-loaded structure of the robot makes it possible to treat multiple targets of the disease, and it is simple to operate, low-cost, and truly non-invasive. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] FIG1 is a schematic diagram, a preparation flow chart, and a principle diagram of a multi-layer magnetic soft robot provided in an embodiment of the present invention.

[0033] FIG2 is a state diagram of a capsule-encapsulated and released multi-layer magnetic soft robot provided by an embodiment of the present invention.

[0034] FIG3 is a schematic diagram showing the principle of unidirectional drug release in a drug-loaded adhesive film according to an embodiment of the present invention.

[0035] FIG4 is a schematic diagram showing the principle of adhesion between the drug-loaded adhesive film and tissue provided by an embodiment of the present invention.

[0036] FIG5 is a diagram showing a specific application example of a multi-layer magnetic soft robot provided by an embodiment of the present invention. DETAILED DESCRIPTION

[0037] The present invention provides a multilayer magnetic soft robot and its preparation and control methods. To make the objectives, technical solutions, and effects of the present invention more clear and explicit, the present invention is further described below. It should be understood that the specific embodiments described herein are merely illustrative of the present invention and are not intended to limit the present invention.

[0038] An embodiment of the present invention provides a multi-layer magnetic soft robot, comprising a top layer, a bottom layer, and a center layer arranged between the top layer and the bottom layer. Each layer comprises a drug-loaded adhesive film and a magnetic flexible substrate. The three-layer structure self-assembles into the multi-layer magnetic soft robot under the magnetic force of the flexible substrate.

[0039] In some embodiments, the structures of the top layer, the center layer, and the bottom layer each include a drug-loaded adhesive film and a magnetic flexible substrate.

[0040] The core of the multi-layer magnetic soft robot of the embodiment of the present invention lies in the design and preparation of each layer structure. As shown in Figure 1, the multi-layer magnetic soft robot consists of a top layer, a center layer and a bottom layer. Each layer structure includes a drug-loaded adhesive film and a flexible substrate with magnetism, which can deliver drugs to multiple targets and achieve continuous and precise release of therapeutic drugs through tissue adhesion. The drug-loaded adhesive film serves as a functional layer for storing drugs and forming adhesion with tissues. The flexible substrate serves as a driving layer and a protective layer, which makes it possible to assemble, move and adhere to the robot.

[0041] In some embodiments, the flexible substrate of the central layer consists of a non-magnetic frame and a magnetic bottom; and the magnetic flexible substrate of the top layer or bottom layer consists of a magnetic frame and a non-magnetic bottom.

[0042] In the present invention, there are two types of flexible substrates: for the center layer, the flexible substrate includes a non-magnetic frame and a magnetic bottom; for the top layer and the bottom layer, the flexible substrate includes a magnetic frame and a non-magnetic bottom. Figure 1b also shows one of the assembly methods of the flexible substrates of the center layer, the top layer and the bottom layer. The flexible substrate also provides multiple functions: first, the flexible substrate acts as a driving layer, which mainly provides magnetic attraction for the self-assembly of multi-layer magnetic soft robots, and can realize corresponding translational movement and tumbling movement in a magnetic field. Each flexible layer can provide a self-assembly method for the robot, and its bonding strength is sufficient to realize the translation and tumbling movement of the robot. Secondly, the flexible substrate acts as a protective layer, and the special design of the frame completely wraps the adhesive film in the middle. Its excellent hydrophobicity ensures the integrity of the drug-loaded adhesive film and avoids leakage of drugs during the adhesion process.

[0043] In some embodiments, the multilayer magnetic soft robot can accurately reach a target location using different motion modes under the influence of an external magnetic field. This is because the flexible layer provides a self-assembly method for the robot, and its bonding strength is sufficient to achieve translational and tumbling motions of the robot.

[0044] In some embodiments, the material of the magnetic base or the magnetic frame comprises ferromagnetic particles, and the material of the non-magnetic base or the non-magnetic frame comprises silica gel.

[0045] In some embodiments, the ferromagnetic particles are neodymium iron boron (NdFeB).

[0046] In some embodiments, the silica gel includes one or more of polydimethylsiloxane (PDMS) and Ecoflex series silica gel.

[0047] Specifically, the Ecoflex series silicone can be selected from Ecoflex 00-10, Ecoflex 00-20, Ecoflex 00-30, Ecoflex 00-35, Ecoflex 00-50, etc., but is not limited thereto.

[0048] The functions of magnetic or non-magnetic bottoms or frames are different, and their materials are also different. The flexible substrate material of a magnetic bottom or frame contains ferromagnetic particles (such as NdFeB), while the flexible substrate of a non-magnetic bottom or frame is made of biocompatible silicone (such as PDMS or Ecoflex series).

[0049] In some embodiments, the material of the drug-loaded adhesive film includes a bioadhesive material and an adjuvant.

[0050] Specifically, the bioadhesive material includes one or more of the Carbopol series, such as Carbopol 910, 934, 934P, 940, 941, 954, etc., or new series thereof; the adjuvant includes hydroxypropyl methylcellulose and poloxamer.

[0051] In the present invention, the drug-loaded adhesive membrane serves as a functional layer for storing drugs and forming adhesion with tissues. Each drug-loaded adhesive layer can achieve tissue adhesion to the corresponding target site, enabling sustained and precise drug release. Therefore, it includes a bioadhesive material capable of forming adhesion with tissues and corresponding adjuvants, such as adhesives, film-forming agents, surfactants, pharmaceutical excipients, and the like. The selection of specific bioadhesive materials and corresponding adjuvants can be specifically considered based on the application scenario of the robot. For example, Figure 1a shows a specific embodiment of a robot primarily for treating gastric ulcers, which utilizes carbopol, a partially cross-linked polyacrylic acid, a bioadhesive material capable of forming adhesion with the gastric mucosa. In addition to carbopol, hydroxypropyl methylcellulose (HPMC) and poloxamer are also added to enhance the plasticity and film-forming properties of the adhesive membrane. Ultimately, each drug-loaded adhesive layer can achieve tissue adhesion with the gastric mucosa, enabling sustained and precise release of drugs for treating gastric ulcers.

[0052] In some embodiments, the drug-loaded adhesive films of the top layer, center layer, and bottom layer of the multi-layer magnetic soft robot can be loaded with the same drug or different drugs.

[0053] Each layer of the robot consists of a drug-loaded adhesive membrane and a flexible substrate, enabling drug delivery to multiple targets and achieving sustained, precise release of therapeutic drugs through tissue adhesion. Each layer of the drug-loaded adhesive membrane can be loaded with the same drug, precisely delivering the same drug to different targets for sustained release. It can also be loaded with different drugs, precisely delivering multiple drugs to different targets for sustained release. It can also achieve layered drug release at different time points for the same target, delivering different drugs to the same target in batches.

[0054] In some embodiments, the multi-layer magnetic soft robot can be encapsulated into a capsule.

[0055] The robot can be rolled up and placed in a conventional pharmaceutical capsule, making it easy to enter the body by swallowing and reach the corresponding target. The capsule then dissolves to release the robot. Figure 2 shows the state diagram of the multi-layer magnetic soft robot during capsule encapsulation and release of the present invention. Figure a shows the capsule encapsulation state of the multi-layer magnetic soft robot, and Figure b shows the capsule release state of the multi-layer magnetic soft robot. In a specific embodiment, the multi-layer magnetic soft robot can be encapsulated in a gastric-soluble capsule, making it easy to enter the stomach by swallowing. In gastric juice, the capsule dissolves to release the robot.

[0056] In some embodiments, the drug-loaded adhesive film performs unidirectional drug release.

[0057] The multilayered magnetic soft robot of this invention features a flexible substrate as a protective layer, and a specially designed frame that completely encloses the adhesive film. Its excellent hydrophobicity ensures the integrity of the drug-loaded adhesive film, preventing drug leakage during the adhesion process. Furthermore, the hydrophobicity of the flexible substrate also ensures unidirectional drug release, as shown in Figure 3.

[0058] An embodiment of the present invention further provides a method for preparing a multi-layer magnetic soft robot, comprising the steps of:

[0059] S10, preparing a magnetic film, a non-magnetic film, and a drug-loaded adhesive film;

[0060] S20, cutting the magnetic film into a magnetic base and a magnetic frame, and cutting the non-magnetic film into a non-magnetic base and a non-magnetic frame;

[0061] S30, assembling a top layer, a center layer, and a bottom layer respectively, wherein the center layer is composed of a non-magnetic frame, a magnetic bottom, and a drug-loaded adhesive film, and the top layer or the bottom layer is composed of a magnetic frame, a non-magnetic bottom, and a drug-loaded adhesive film;

[0062] S40, placing the assembled top layer, center layer and bottom layer in a magnetic field for magnetization, and the three-layer structure self-assembles into the multi-layer magnetic soft robot under the action of the magnetic force.

[0063] Figure 1 illustrates a process for preparing a multilayer magnetic soft robot according to an embodiment of the present invention. First, a magnetic film, a non-magnetic film, and a drug-loaded adhesive film are prepared (Figure a). The materials of these films can be selected based on specific needs. For example, the magnetic film is prepared using ferromagnetic NdFeB particles and biocompatible silicone PDMS, while the non-magnetic PDMS film is prepared using silicone PDMS. Laser shearing is then performed to obtain a magnetic base, a magnetic frame, a non-magnetic base, and a non-magnetic frame. The adhesive film is prepared using carbopol, hydroxypropyl methylcellulose (HPMC), and poloxamer. Next, the top layer, center layer, and bottom layer are assembled separately (Figure b). After plasma cleaning of each film, the center layer is composed of the non-magnetic frame, magnetic base, and drug-loaded adhesive film, while the top or bottom layer is composed of the magnetic frame, non-magnetic base, and drug-loaded adhesive film. Finally, the assembled top layer, center layer, and bottom layer are placed in a magnetic field for magnetization. Under the influence of the magnetic force, the three-layer structure self-assembles into the multilayer magnetic soft robot (Figure c).

[0064] In some specific embodiments, the magnetic film is composed of ferromagnetic particles NdFeB and PDMS, and its preparation method is: first, NdFeB:PDMS = 2:1 are mixed and stirred to obtain a magnetic slurry, the magnetic slurry is poured on the bottom of a culture dish, and uncured magnetic films of different thicknesses are obtained by spin coating, which are placed on a hot plate at 60°C and baked for 4 hours to obtain a cured magnetic film.

[0065] In some specific embodiments, the PDMS film is obtained by spin coating and heating curing in the same manner: liquid PDMS is poured on the bottom of a culture dish, and uncured magnetic films of different thicknesses are obtained by spin coating, which are then placed on a hot plate at 60°C and baked for 4 hours to obtain a cured PDMS film.

[0066] In some specific embodiments, the adhesive film is prepared by first weighing Carbopol, Poloxamer, and HPMC in a ratio of 1:1:1, then pouring the mixture into 30 mL of deionized water and magnetically stirring until a homogeneous solution is formed. The solution is then poured into a Petri dish and dried in a 37°C oven to produce the adhesive film.

[0067] An embodiment of the present invention further provides a control method for the multi-layer magnetic soft robot, comprising the steps of:

[0068] S100, providing a multi-layer magnetic soft robot, wherein the multi-layer magnetic soft robot comprises a top layer, a center layer, and a bottom layer, wherein the structure of each layer comprises a drug-loaded adhesive film and a magnetic flexible substrate;

[0069] S200, applying magnetic force to the robot through a permanent magnet to control it to move to target point one;

[0070] S300, fixing the permanent magnet so that the drug-loaded adhesive film on the bottom layer of the robot adheres to the target;

[0071] S400: Flip the permanent magnet to change the direction of the magnetic field, so that the robot can flip and separate from the bottom layer.

[0072] S500, continue to maintain the direction of the permanent magnet, and control the robot that has left the bottom layer to move to target point 2;

[0073] S600, fixing the permanent magnet so that the drug-loaded adhesive film on the top layer of the robot adheres to the second target;

[0074] S700: Flip the permanent magnet to change the direction of the magnetic field, causing the robot to flip and separate from the top layer.

[0075] S800: Continue to maintain the direction of the permanent magnet and control the robot that has separated from the bottom and top layers to move to target point three;

[0076] S900. Fix the permanent magnet so that the drug-loaded adhesive film on the center layer of the robot adheres to target point three.

[0077] The present invention proposes a control method for multi-target drug delivery based on a multi-layer magnetic soft robot, which uses the multi-layer magnetic soft robot to achieve precise targeting of multiple targets in the body. The specific implementation steps are as follows:

[0078] a. Preparation of a multi-layer magnetic soft robot: Prepare the multi-layer magnetic soft robot in advance. The robot is originally in sheet form due to the magnetic attraction between its layers, and is encapsulated into a capsule by bending.

[0079] b. The robot is swallowed and released after the capsule dissolves. A permanent magnet is used to apply magnetic force to the magnetic multilayer soft robot, causing it to adhere to the wall and move to the target point in a translational manner.

[0080] c. Fixed permanent magnets provide the pressing force required to form tissue adhesion. Hydrogen bonds are formed between the adhesion film and the tissue in a very short time, achieving close tissue adhesion at the target site.

[0081] d. Flip the permanent magnet to change the direction of the magnetic field. Under the action of the magnetic torque, the robot realizes flipping motion and completes separation from the bottom layer.

[0082] e. Maintaining the orientation of the permanent magnet, continue dragging the robot toward target point 2, slowly adjusting the permanent magnet until the robot completely covers the target point. Similarly, position the permanent magnet to allow the adhesive film to adhere to the tissue surrounding the target point. Because the adhesive film's surface may adhere to mucosa and gastric fluid during delivery, which affects its adhesion strength, the second adhesion takes longer than the first.

[0083] f. Then flip the magnet to change the direction of the magnetic field, leaving the top layer on target two, and then control the robot to go to target three, and finally complete the adhesion of target three under the action of the magnetic field.

[0084] g. After the third application, the drug-loaded adhesive film will gradually release the drug toward the lesion. Due to the presence of the flexible substrate, the drug is released in one direction.

[0085] Throughout the delivery process, each layer of the adhesive film forms a tight tissue adhesion to the tissue. The principle diagram of tissue adhesion is shown in Figure 4. Magnetic force provides the compressive force required for tissue adhesion, and hydrogen bonds form between the adhesive film and tissue in a very short time, achieving tight tissue adhesion at the target site. After drug release is complete, the adhesive film naturally disintegrates. Because the flexible substrate lacks tissue adhesion, it naturally falls off and is excreted from the body with feces, truly providing a single-shot multi-target delivery solution.

[0086] An embodiment of the present invention further provides an application of a multi-layer magnetic soft robot, wherein the multi-layer magnetic soft robot is applied to the preparation of multi-target therapeutic drugs.

[0087] In some embodiments, the multi-layer magnetic soft robot is used to prepare drugs for multi-target treatment of gastric inflammation or gastric ulcer.

[0088] Figure 5 illustrates a specific application example of the present invention, in which the multi-layer magnetic soft robot is used to prepare a multi-target therapeutic drug for multiple gastric ulcers. The drug is a gastric-soluble capsule encapsulated with the multi-layer magnetic soft robot, allowing for easy delivery to the stomach. The robot consists of a three-layer structure, each containing a magnetically flexible and drug-loaded adhesive membrane. The three-layer structure self-assembles under magnetic attraction and can be rolled up and placed into a conventional pharmaceutical capsule. The specific implementation method involves swallowing the encapsulated magnetic soft robot into the stomach. Under the influence of gastric fluid, the capsule dissolves, releasing the magnetic soft robot. The robot is then driven by a magnetic field to move to target point one. The magnetic field is fixed, and the adhesive membrane adheres to the gastric mucosa under the action of a gradient force. The direction of the magnetic field is then changed, separating the robot from the adhered layer structure, completing the delivery to target point one. The delivery to target point two is completed in the same manner. Finally, the magnetic robot is delivered to target point one, where it adheres under the influence of magnetic force. The drug-loaded adhesive membrane then begins to slowly release the drug. The presence of the adhesive enables the drug to remain at its target site for extended periods of time. Furthermore, the multi-layered drug-loaded structure enables multi-target treatment. This invention develops a multi-target therapeutic drug for gastric ulcers, providing a non-invasive approach to treating gastric ulcers. Compared to existing treatments for gastric ulcers and gastric perforation, this invention achieves a non-invasive approach to treating related diseases, is simple to operate, and is low-cost, possessing significant practical significance and potential for application.

[0089] The following is a further explanation of a multi-layer magnetic soft robot and its preparation method and control method of the present invention through specific embodiments:

[0090] Example 1

[0091] Prepare magnetic film, PDMS film and adhesive film respectively

[0092] The magnetic film is composed of ferromagnetic NdFeB particles and PDMS. A magnetic slurry is first prepared by mixing NdFeB:PDMS in a ratio of 2:1. This slurry is then poured onto the bottom of a Petri dish and spin-coated to produce uncured magnetic films of varying thicknesses. Cured magnetic films are then baked on a 60°C hotplate for 4 hours. PDMS films are similarly spin-coated and heat-cured. The adhesive film is prepared as follows: Carbopol, Poloxamer, and HPMC are weighed in a 1:1:1 ratio and poured into 30 mL of deionized water. The mixture is magnetically stirred until a homogeneous solution is formed. The solution is then poured into a Petri dish and dried in a 37°C oven to produce the corresponding adhesive film.

[0093] Example 2

[0094] The multilayer magnetic soft robot consists of three layers: a top layer, a center layer, and a bottom layer. The magnetic base, magnetic frame, non-magnetic base, non-magnetic frame, and adhesive film required for each layer are laser cut from the magnetic film, PDMS film, and adhesive film provided in Example 1. The magnetic base, non-magnetic frame, and adhesive film constitute the center layer, which are assembled after plasma treatment. The non-magnetic base, magnetic frame, and adhesive film constitute the top and bottom layers, which are assembled after plasma treatment. The three layers are then stacked together and placed in a strong magnetic field for magnetization, resulting in the three layers having the same magnetization pattern, allowing self-assembly without external interference.

[0095] Example 3

[0096] The multi-layer magnetic soft robot prepared in Example 2 was subjected to a dynamic tissue adhesion effect test: a clamp was used to fix the two ends of the isolated pig stomach, and the single-layer structure (top layer / bottom layer) of the robot was adhered to the isolated pig stomach tissue. Subsequently, a tensile reciprocating experiment was performed on the pig stomach tissue. During the entire reciprocating motion, the pig stomach and the layer structure were immersed in artificial gastric juice. The results showed that when the frequency of the reciprocating motion was 0.25Hz, the retention time of the layer structure was 25h. The peristaltic frequency of human stomach is 0.05Hz, which shows that the multi-layer magnetic soft robot can be retained in the human body for a long time and has the potential to be used for multi-target therapeutic drug delivery and sustained release.

[0097] In summary, the present invention provides a multilayer magnetic soft robot and its preparation and control methods. The multilayer magnetic soft robot consists of a three-layer structure, including a top layer, a center layer, and a bottom layer. Each layer contains a magnetic flexible substrate and a drug-loaded adhesive film. The three-layer structure self-assembles under the action of magnetic attraction and can be rolled up and placed into a conventional pharmaceutical capsule. Each layer of the robot structure contains a drug-loaded adhesive film, which can deliver drugs to multiple targets, making multi-target treatment possible. Moreover, due to the presence of an adhesive, it can achieve tissue adhesion with the target, allowing the drug to remain in the target for a long time, making it possible to release the drug continuously and accurately, and achieving long-term treatment. The magnetic flexible substrate provides a self-assembly method for the robot, and its bonding strength is sufficient to achieve translational and tumbling motion of the robot, allowing the robot to accurately reach the target position in different motion modes under the action of an external magnetic field. Ultimately, the multilayer drug-loaded structure of the robot makes it possible to treat multiple targets of disease, and it is simple to operate, low-cost, and truly non-invasive.

[0098] It should be understood that the application of the present invention is not limited to the above examples. For those skilled in the art, improvements or changes can be made based on the above description. All these improvements and changes should fall within the scope of protection of the claims attached to the present invention.

Claims

1. A multi-layer magnetic soft robot, characterized in that: It comprises a top layer, a bottom layer, and a center layer arranged between the top layer and the bottom layer. Each layer comprises a drug-loaded adhesive film and a magnetic flexible substrate. The three-layer structure self-assembles into the multi-layer magnetic soft robot under the magnetic force of the flexible substrate.

2. The multi-layer magnetic soft robot according to claim 1, characterized in that: The flexible substrate of the central layer is composed of a non-magnetic frame and a magnetic bottom; the flexible substrate of the top layer or the bottom layer is composed of a magnetic frame and a non-magnetic bottom.

3. The multi-layer magnetic soft robot according to claim 2, characterized in that: The material of the magnetic bottom or the magnetic frame includes ferromagnetic particles, and the material of the non-magnetic bottom or the non-magnetic frame includes silica gel.

4. The multi-layer magnetic soft robot according to claim 3, characterized in that: The ferromagnetic particles are neodymium iron boron, and the silica gel includes one or more of polydimethylsiloxane and Ecoflex series silica gel.

5. The multi-layer magnetic soft robot according to claim 1, characterized in that: The material of the drug-loaded adhesive film includes bioadhesive material and adjuvant.

6. The multi-layer magnetic soft robot according to claim 1, characterized in that: The drug-loaded adhesive films of the top layer, the center layer and the bottom layer are loaded with the same drug, or are respectively loaded with different drugs.

7. A method for preparing a multilayer magnetic soft robot as claimed in any one of claims 1 to 6, characterized in that: Includes steps: Preparation of magnetic films, non-magnetic films and drug-loaded adhesive films; Cutting the magnetic film into a magnetic bottom and a magnetic frame, and cutting the non-magnetic film into a non-magnetic bottom and a non-magnetic frame; Assembling a top layer, a center layer and a bottom layer respectively, wherein the center layer is composed of a non-magnetic frame, a magnetic bottom and a drug-carrying adhesive film, and the top layer or the bottom layer is composed of a magnetic frame, a non-magnetic bottom and a drug-carrying adhesive film; The assembled top layer, center layer and bottom layer are placed in a magnetic field for magnetization, and the three-layer structure is self-assembled into the multi-layer magnetic soft robot under the action of the magnetic force.

8. A control method for a multi-layer magnetic soft robot as claimed in any one of claims 1 to 6, characterized in that: Includes steps: A multilayer magnetic soft robot is provided, wherein the multilayer magnetic soft robot comprises a top layer, a center layer and a bottom layer, and the structure of each layer comprises a drug-loaded adhesive film and a magnetic flexible substrate; Apply magnetic force to the robot through a permanent magnet to control it to move to target point one; Fix the permanent magnet so that the drug-loaded adhesive film on the bottom layer of the robot adheres to the target point; Flip the permanent magnet to change the direction of the magnetic field, so that the robot can flip and detach from the bottom layer. Continue to maintain the direction of the permanent magnet and control the robot that has left the bottom layer to move to target point 2; Fix the permanent magnet so that the drug-loaded adhesive film on the top layer of the robot adheres to the second target; Flip the permanent magnet to change the direction of the magnetic field, so that the robot can flip and detach from the top layer. Continue to maintain the direction of the permanent magnet and control the robot that has separated from the bottom and top layers to move to target point three; The permanent magnet is fixed so that the drug-loaded adhesive film of the center layer of the robot adheres to target point three.

9. An application of a multi-layer magnetic soft robot, characterized in that: The multilayer magnetic soft robot as described in any one of claims 1 to 6 is applied to the preparation of multi-target therapeutic drugs.

10. The use according to claim 9, characterized in that: The multi-layer magnetic soft robot is applied to the preparation of drugs for multi-target treatment of gastric inflammation or gastric ulcer.

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