Drug delivery system, microrobot, and microrobot preparation method

Abstract

The present invention discloses a microrobot, including a chassis, a groove is provided on one side of the chassis, and more air is retained in the groove. When the microrobot of the present invention is in a viscous blood environment, the fluid flows through the surface of the microrobot, forming a solid-gas-liquid three-phase interface at the groove, enhancing the hydrophobic effect of the microrobot, thereby reducing the motion resistance of the microrobot in the blood environment and improving the motion efficiency of the microrobot; at the same time, a drug loading cabin is provided on the other side of the chassis, and the hollow part of the drug loading cabin can be used to carry drugs. The protruding drug loading cabin ensures that the drug loading cabin has a certain drug loading space. After the microrobot reaches the target tissue position, the chassis made of degradable hydrogel is degraded to release the drug, completing targeted drug delivery. At the same time, the present invention also provides a drug delivery system comprising the above-mentioned microrobot and a preparation method of the above-mentioned microrobot.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices and peripheral supporting facilities thereof, and in particular to a drug delivery system, a microrobot and a method for preparing the microrobot. Background Art

[0002] Inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease are on the rise worldwide, posing significant challenges to patients' quality of life and health. While traditional treatments, such as systemic drug administration, can alleviate inflammatory symptoms, they are also associated with issues such as widespread drug distribution throughout the body, nonspecific effects on normal tissues, and rapid drug clearance from the bloodstream.

[0003] In recent years, the application of micro-magnetically controlled robots in the precision treatment of diseases such as inflammation has attracted widespread attention. Driven by external magnetic fields, these micro-magnetically controlled robots can precisely manipulate and navigate within the body. Their non-invasive, minimally invasive, and highly directional properties make them a disruptive new therapeutic approach for the precision treatment of inflammatory diseases.

[0004] Currently, there are a variety of magnetically controlled microrobots for targeted therapy. Most of these are designed for microscale, high-viscosity environments, with magnetic particles incorporated into or within the robot's surface, ultimately enabling multimodal motion driven by a passive magnetic field. However, existing magnetically controlled microrobots for targeted therapy suffer from the following issues: The microrobot's structural design only considers ensuring efficient motion at the microscale, but the structure struggles to achieve drug delivery. Furthermore, during actual motion, due to the viscous environment of blood, the current robot's structural design increases resistance to movement in the blood, resulting in unstable motion and reduced efficiency.

[0005] Therefore, how to change the current situation in which microrobots cannot balance drug delivery and movement efficiency has become an urgent problem to be solved by those skilled in the art. Summary of the Invention

[0006] The purpose of the present invention is to provide a drug delivery system, a microrobot and a method for preparing a microrobot to solve the problems existing in the above-mentioned prior art, so that the microrobot can improve the movement efficiency while achieving drug delivery, thereby improving the working reliability of the drug delivery system.

[0007] To achieve the above object, the present invention provides the following solution: The present invention provides a micro robot, comprising:

[0008] A chassis having a groove on one side and a protruding drug-loading chamber on the other side, wherein the drug-loading chamber is a hollow structure, the hollow portion of the drug-loading chamber is used to carry drugs, and after the microrobot reaches the target tissue location, the drug-loading chamber can release the drugs; the chassis is made of degradable hydrogel.

[0009] Preferably, the chassis is in the shape of a regular polygonal column, the groove is in the shape of a cylinder, and the two are coaxially arranged; the medicine loading cabin is in the shape of a spherical or ellipsoidal ball.

[0010] Preferably, the microrobot further comprises:

[0011] A tentacle, one end of which is connected to the side of the chassis, and the other end of which extends in a direction away from the center of the chassis. The tentacle is a hollow structure, and the hollow part of the tentacle can carry drugs; the tentacle is made of degradable hydrogel.

[0012] Preferably, one side of the tentacle has a protrusion, and the protrusion and the drug-carrying cabin are located on the same side of the microrobot.

[0013] Preferably, the protrusion is spherical; there are multiple protrusions, and the protrusions are arranged in an array on the tentacle.

[0014] Preferably, there are multiple tentacles, and the multiple tentacles are evenly distributed around the axis of the chassis.

[0015] Preferably, the tentacle is a conical structure, the end of the tentacle with a larger diameter is connected to the chassis and the connection between the two is chamfered, and the end of the tentacle with a smaller diameter is arranged in a direction away from the chassis.

[0016] The present invention also provides a drug delivery system, comprising the aforementioned microrobot and a control unit capable of controlling the motion state of the microrobot.

[0017] Preferably, the microrobot has a magnetic structure layer on the outside, and the control unit controls the motion state of the microrobot using a magnetic control method.

[0018] The present invention also provides a method for preparing the microrobot, which uses hydrogel to prepare the microrobot by photolithography.

[0019] Compared with the prior art, the present invention has achieved the following technical effects: the microrobot of the present invention includes a chassis, a groove is provided on one side of the chassis, and a protruding drug-loading cabin is provided on the other side. The drug-loading cabin is a hollow structure, and the hollow part of the drug-loading cabin is used to carry drugs, and after the microrobot reaches the target tissue position, the drug-loading cabin can release the drugs; the chassis is made of degradable hydrogel.

[0020] The microrobot of the present invention is provided with a groove on one side of the chassis, where more air is retained. When the microrobot of the present invention is in a viscous blood environment, the fluid flows through the surface of the microrobot, forming a solid-gas-liquid three-phase interface at the groove, enhancing the hydrophobic effect of the microrobot, thereby reducing the motion resistance of the microrobot in the blood environment and improving the motion efficiency of the microrobot; at the same time, a drug loading cabin is provided on the other side of the chassis, and the hollow part of the drug loading cabin can be used to carry drugs. The protruding drug loading cabin ensures that the drug loading cabin has a certain drug loading space. After the microrobot reaches the target tissue position, the chassis made of degradable hydrogel degrades, releases the drug, and completes targeted drug delivery. The microrobot of the present invention improves the motion efficiency of the microrobot while achieving drug loading.

[0021] At the same time, the present invention also provides a drug delivery system, comprising the above-mentioned microrobot and a control unit, wherein the control unit can control the motion state of the microrobot so that the microrobot can smoothly reach the target tissue position, thereby improving drug delivery reliability.

[0022] In addition, the present invention also provides a method for preparing the above-mentioned microrobot, which adopts photolithography and uses degradable hydrogel to prepare the microrobot, so that the microrobot can smoothly degrade and release drugs after reaching the target tissue location. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0024] Figure 1 An axonometric diagram of the microrobot disclosed in an embodiment of the present invention;

[0025] Figure 2 This is a front view of the micro robot disclosed in an embodiment of the present invention;

[0026] Figure 3 A side view of the microrobot disclosed in an embodiment of the present invention;

[0027] Figure 4 This is a rear view of the microrobot disclosed in an embodiment of the present invention.

[0028] Among them, 1 is the chassis, 2 is the groove, 3 is the medicine compartment, 4 is the tentacle, and 5 is the protrusion. DETAILED DESCRIPTION

[0029] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0030] The purpose of the present invention is to provide a drug delivery system, a microrobot and a method for preparing a microrobot to solve the problems existing in the above-mentioned prior art, so that the microrobot can improve the movement efficiency while achieving drug delivery, thereby improving the working reliability of the drug delivery system.

[0031] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0032] The present invention provides a microrobot, comprising a chassis 1, one side of the chassis 1 having a groove 2 and the other side having a protruding drug-loading cabin 3, the drug-loading cabin 3 being a hollow structure, the hollow part of the drug-loading cabin 3 being used to carry drugs, and after the microrobot reaches the target tissue position, the drug-loading cabin 3 can release the drugs; the chassis 1 is made of degradable hydrogel.

[0033] The microrobot of the present invention has a groove 2 set on one side of the chassis 1. A large amount of air is retained in the groove 2. When the microrobot of the present invention is in a viscous blood environment, the fluid flows through the surface of the microrobot, forming a solid-gas-liquid three-phase interface at the groove 2, enhancing the hydrophobic effect of the microrobot, thereby reducing the movement resistance of the microrobot in the blood environment and improving the movement efficiency of the microrobot. At the same time, a drug loading chamber 3 is set on the other side of the chassis 1. The hollow portion of the drug loading chamber 3 can be used to carry drugs. The protruding drug loading chamber 3 also ensures that the drug loading chamber 3 has a certain amount of drug loading space. After the microrobot reaches the target tissue location, the chassis 1 made of degradable hydrogel degrades, releasing the drug, completing targeted drug delivery. At the same time, the chassis 1 made of hydrogel enables the microrobot to deform and adapt to various shapes of blood vessels, enhancing the movement performance of the microrobot while improving the adaptability of the microrobot. The microrobot of the present invention improves the movement efficiency of the microrobot while achieving drug loading.

[0034] In this specific embodiment, the chassis 1 is in the shape of a regular polygonal column, and the groove 2 is cylindrical, avoiding dead corners that could cause fluid accumulation. The chassis 1 and groove 2 are coaxially arranged to improve the structural stability of the chassis 1, thereby further improving the motion performance of the microrobot. It should also be noted that the drug loading chamber 3 is spherical or ellipsoidal, increasing the drug loading space in the hollow portion of the drug loading chamber 3. At the same time, the spherical or ellipsoidal structure helps reduce the motion resistance of the microrobot. In addition, in actual applications, multiple grooves 2 can be provided on the chassis 1 to meet different working conditions and improve the flexibility and adaptability of the microrobot.

[0035] Specifically, the microrobot of the present invention further includes a tentacle 4, one end of which is connected to the side of the chassis 1, and the other end of the tentacle 4 extends in a direction away from the center of the chassis 1. The tentacle 4 is a hollow structure, and the hollow part of the tentacle 4 can carry drugs; the tentacle 4 is made of a degradable hydrogel. The microrobot of the present invention is provided with a tentacle 4 surrounding the chassis 1 on the basis of the chassis 1, which enhances the structure and movement stability of the microrobot, and the hollow part of the tentacle 4 can also be used to carry drugs, thereby enhancing the drug carrying capacity of the microrobot. The tentacle 4 is also made of a degradable hydrogel. When it reaches the target tissue location, the tentacle 4 degrades and releases the drug; in addition, during the movement of the microrobot, when it moves to a smaller area of ​​space, the tentacle 4 can produce a certain deformation, allowing the microrobot to pass smoothly, thereby improving the movement reliability of the microrobot.

[0036] It should also be emphasized that one side of the tentacle 4 has a protrusion 5, and the protrusion 5 and the drug loading chamber 3 are located on the same side of the microrobot. Protrusions 5 are provided on the surface of the tentacle 4 to increase the roughness and surface area of ​​the surface of the tentacle 4. When the fluid flows through the protrusion 5, a solid-gas-liquid three-phase interface is formed, thereby enhancing the hydrophobic properties of the tentacle 4, thereby reducing the movement resistance encountered by the microrobot when blood flows through the tentacle 4, and improving the movement efficiency of the microrobot.

[0037] In other embodiments of the present invention, the protrusions 5 can be spherical or ellipsoidal to reduce motion resistance and prevent liquid accumulation. The number of protrusions 5 can be multiple to further increase the surface area of ​​the tentacle 4. In practical applications, the protrusions 5 can be arranged in an array on the tentacle 4, and a circular or rectangular array can be selected according to actual working conditions.

[0038] Accordingly, there are multiple tentacles 4, which further enhance the drug-carrying capacity and movement performance of the microrobot. The multiple tentacles 4 are evenly distributed around the axis of the chassis 1, which improves the structural stability and force uniformity of the microrobot.

[0039] In other specific embodiments of the present invention, the tentacle 4 is a conical structure, and the end with a larger diameter of the tentacle 4 is connected to the chassis 1 to enhance the overall structural strength of the micro robot. The connection between the tentacle 4 and the chassis 1 is chamfered to reduce the resistance to fluid passage, thereby enhancing the movement performance of the micro robot. The end with a smaller diameter of the tentacle 4 is set in a direction away from the chassis 1, and the end face of the end with a smaller diameter of the tentacle 4 is set as an arc surface to further reduce the movement resistance of the micro robot.

[0040] In this embodiment, the microrobot is fabricated from alginate hydrogel. Due to the uniform density distribution of the cross-linked network within the microrobot and the more uniform and consistent strain gradient, it can undergo repeated deformations without structural damage during contraction. In practical applications, other types of degradable hydrogels could be used, and the number and arrangement of tentacles 4 and protrusions 5 could be adjusted according to actual working conditions to enhance the microrobot's flexibility and adaptability.

[0041] It should also be noted that in actual applications, immune cells can be embedded on the base for targeted identification of antigens. When the microrobot reaches the target tissue location, the immune cells embedded on the base recognize the antigen and bind to it; because the pH and temperature of the target tissue area are different from those of the normal area, the microrobot degrades and releases the drug at the target tissue location, completing the drug delivery at the target tissue location.

[0042] More specifically, the present invention also provides a drug delivery system comprising the aforementioned microrobot and a control unit capable of controlling the motion state of the microrobot. In this specific embodiment, the microrobot has a magnetic structural layer on its exterior, and the control unit uses magnetic control to control the motion state of the microrobot. When the control unit applies a rotating magnetic field externally, the magnetic force acting on the microrobot's magnetic structural layer drives the microrobot into motion. When the control unit applies a rotating magnetic field, the microrobot rolls forward; when a gradient magnetic field is applied, the microrobot moves forward in a straight line.

[0043] The present invention also provides a method for preparing the microrobot, which adopts a photolithography method and utilizes hydrogel to prepare the microrobot.

[0044] The microrobot and the method for preparing the microrobot of the present invention are further explained below through specific embodiments.

[0045] Example 1

[0046] In this embodiment, the chassis 1 of the microrobot is configured as a regular octagonal prism structure, the circumscribed circle diameter of the chassis 1 is 55μm-65μm, the height is 30μm-50μm, the outer diameter of the groove 2 is 45μm-50μm, the inner diameter is 40μm-42μm, and the depth is 3μm-5μm; the number of tentacles 4 is eight, which are respectively arranged on the eight side elevations of the chassis 1, the maximum diameter of the tentacle 4 is 30μm-35μm, the minimum diameter is 5μm-10μm, and the length is 260μm; each tentacle 4 is provided with two rows of protrusions 5, each row of protrusions 5 is arranged along the length direction of the tentacle 4, the number of protrusions 5 in each row is 8, the height of the protrusion 5 is 2μm, and the spacing between adjacent protrusions 5 is 6μm.

[0047] The method for preparing the microrobot of this embodiment includes the following steps:

[0048] S1: The chassis 1 and tentacle 4 of the microrobot are manufactured using a microelectrode method by processing photoresist on a SnO2:F (FTO) plate to form the chassis 1 and tentacle 4 of alginate hydrogel material;

[0049] S2: The step of coating the chassis 1 and the tentacle 4 with a magnetic film to form a magnetic structural layer, using N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid (HEPES) and chemical bonding to immerse the chassis 1 and the tentacle 4 in a uniform dispersion of magnetic nanoparticles containing PVP@SiO2 (a composite material of polyvinyl pyrrolidone combined with dioxide particles) and PVP@Fe3O4 (a composite material of polyvinyl pyrrolidone combined with ferrosoferric oxide particles);

[0050] PVP@SiO2 exhibits excellent drug-carrying capacity and controlled-release properties. Due to the porous structure of SiO2, drug molecules can be adsorbed within the pores, and the encapsulation of PVP stabilizes and controls drug release. PVP@Fe3O4 also exhibits excellent magnetic properties, enabling the use of magnetic fields to drive the microrobot's motion.

[0051] S3: Magnetization step: A single-stage electromagnet uniform magnetic field magnetization system is used to magnetize the microrobot in a single direction. This is because PVP@Fe3O4 magnetic nanoparticles are a soft magnetic material with low coercivity and high magnetic permeability, making them easily magnetized and demagnetized in a magnetic field.

[0052] Specifically, S1 includes:

[0053] (1) Octagonal electrode production

[0054] S111: Baking: Use a pipette to draw 1 ml of liquid from the photoresist SZ2080 and drop it onto the center of an ultra-clean microscope cover glass. Next, adjust the hot plate temperature T to 1°C and perform a pre-baking treatment for 2 minutes to prevent the formation of bubbles. Subsequently, increase the hot plate temperature T to 2°C and continue baking for 3 minutes.

[0055] S112: Processing: After aligning the optical path, the FTO board is placed on a three-dimensional piezoelectric platform. By adjusting the position of the focal plane and selecting appropriate laser energy, laser scanning processing of the octagonal electrode pattern is performed.

[0056] S113: Development: Wipe the back of the sample clean, clamp it with a clamp, and place it in n-propanol for development for 3 hours. The part not covered by the photoresist will be washed away, forming an octagonal electrode pattern.

[0057] (2) Electrodeposition

[0058] S121: Place electrodes on both sides of the FTO layer and connect a power supply to apply a constant current, the current I is 1A, and the maintenance time t is 4 minutes.

[0059] S122: Set the current density to 1A / m 2 , current is passed through the electrolytic cell to perform water electrolysis reaction, during which the temperature T is maintained at 3 °C and the duration t is 5 minutes to produce O 2- and H + ion.

[0060] S123: During the electrolysis reaction, observe the H generated on the surface of the anode plate. + ions and measure the pH value of the solution until the pH value of the solution is x1. At this time, by controlling the temperature of the heating device, adjust the temperature T of the electrolysis reaction to 1°C and the electrolysis current I to 2A, so that H + The ions reacted fully with the CaCO3 particles and were kept for 6 minutes before cooling. Since the tips of the octagonal pattern have a higher current density, this leads to a higher degree of local cross-linking during the electrolysis process.

[0061] (3) Preparation of alginate hydrogel

[0062] S131: 5 ml of gelatin solution is dripped into the electrolytic cell container and heated to 4°C to promote dissolution of the gelatin. During the heating process, the gelatin solution is continuously stirred until the gelatin is completely dissolved into a particle-free viscous liquid. The heating time t is 7 minutes.

[0063] S132: Accurately weigh 2 ml of MA solution (L) from the MA solution and add it dropwise to the gelatin solution at a rate of 1 mL / min. During the addition process, keep the solution temperature stable at 5°C and use a stirrer to stir continuously for 8 minutes to ensure sufficient mixing and reaction to form a gel network structure.

[0064] S133: Use N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid (HEPES) buffer to wash and separate the alginate hydrogel network structure remaining on the electrode.

[0065] S134: Prepare HEPES buffer, ensuring a concentration of 1 mol / L, maintaining a temperature of 6°C, and a washing time of 9 minutes. Pour the HEPES buffer onto the electrode at a flow rate of 2 mL / min for 10 minutes to remove residual salt ions and other impurities, thereby obtaining an alginate hydrogel.

[0066] (4) Hydrogel shrinkage and expansion

[0067] S141: Immerse the washed alginate hydrogel microstructure in a CaCl2 solution, set the concentration C of the CaCl2 solution to 3 mol / L, and maintain a suitable temperature and time to allow the alginate hydrogel microstructure to react with the CaCl2 solution. 2+ Ionic cross-linking reaction occurs.

[0068] S142: Control the duration t of the cross-linking reaction to 11 minutes to ensure that the gel microstructure shrinks into a gel form. Remove the shrunken gel from the CaCl2 solution and transfer it to a sodium citrate solution.

[0069] S143: Adjust the concentration C of sodium citrate solution to 4 mol / L, and control the replacement of Ca 2+ The time t of ions is 12 min, which makes the gel structure swell.

[0070] More specifically, S2 includes:

[0071] S211: Preparation of magnetic particle solution: Weigh 1 gram of PVP@SiO2 (a composite material of polyvinyl pyrrolidone and silica particles) and 2 grams of PVP@Fe3O4 (a composite material of polyvinyl pyrrolidone and ferrosoferric oxide particles) and introduce them into a container. Place the container in a high-speed cyclotron oscillator and set the high-speed mixing conditions. Mix at high speed for 8 seconds in the high-speed cyclotron oscillator to ensure that the magnetic particles are evenly dispersed in the solution. After the mixing process is completed, a magnetic solution mother liquor with a concentration of 2% is obtained.

[0072] S212: Coating the microrobot with magnetic particles: Prepare the prepared chassis 1 and tentacle 4. Use a pipette to draw 3 ml of the magnetic solution stock solution. Drop the magnetic solution stock solution onto the chassis 1 and tentacle 4, ensuring even coverage. Place the microrobot coated with magnetic particles on a shaker at room temperature and perform appropriate mixing to ensure that the magnetic particles are evenly distributed on the microrobot surface.

[0073] Furthermore, S3 includes:

[0074] S311: Positioning of the microrobot: The microrobot is accurately placed in the center area of ​​the single-axis electromagnet system at an angle that matches the generated magnetic field.

[0075] S312: Magnetic Field Magnetization: A 1A current is passed through the single-pole electromagnetic coil system to generate a uniform magnetic field. This is maintained for 6 minutes, exposing the microrobot to the magnetic field to complete the magnetic field magnetization process.

[0076] The microrobot of the present invention has a chassis 1 with a drug loading cabin 3 to realize drug loading and drug release of the microrobot; the chassis 1 has a groove 2, and the tentacle 4 has a protrusion 5, which can improve the surface hydrophobicity of the microrobot, thereby increasing the movement speed of the microrobot. Under the premise of drug loading, the adaptability of the microrobot to the low Reynolds number liquid environment is effectively improved; at the same time, the microrobot of the present invention is made of biocompatible hydrogel material, which can be highly adaptable to the living environment of the organism and avoid biological rejection; the size of the microrobot is smaller than the average diameter of human blood vessels, and can be used in minimally invasive surgery. It can penetrate into the tiny blood vessels of the heart and brain for targeted drug delivery.

[0077] The present invention uses specific examples to illustrate the principles and implementation methods of the present invention. The above examples are only intended to help understand the method and core concept of the present invention. At the same time, those skilled in the art will find that the specific implementation methods and application scopes may vary based on the concept of the present invention. In summary, the contents of this specification should not be construed as limiting the present invention.

Claims

1. A micro robot, characterized in that: include: A chassis having a groove on one side and a protruding drug-carrying chamber on the other side. The drug-carrying chamber is a hollow structure. The hollow portion of the drug-carrying chamber is used to carry drugs, and the drug-carrying chamber can release drugs after the microrobot reaches the target tissue location. The chassis is made of degradable hydrogel; The chassis is in the shape of a regular polygonal column, the groove is in the shape of a cylinder, and the two are coaxially arranged; the drug loading cabin is in the shape of a sphere or an ellipsoid; It also includes a tentacle, one end of which is connected to the side of the base, and the other end of which extends away from the center of the base. The tentacle is a hollow structure, and the hollow part of the tentacle can carry drugs; the tentacle is made of degradable hydrogel; One side of the tentacle has a protrusion, and the protrusion and the drug-carrying capsule are located on the same side of the microrobot; The protrusion is spherical; there are multiple protrusions, and the protrusions are arranged in an array on the tentacle.

2. The microrobot according to claim 1, wherein: There are multiple tentacles, and the multiple tentacles are evenly distributed around the axis of the chassis.

3. The microrobot according to claim 1, wherein: The tentacle is a conical structure, the end of the tentacle with a larger diameter is connected to the chassis and the connection between the two is chamfered, and the end of the tentacle with a smaller diameter is arranged in a direction away from the chassis.

4. A drug delivery system, characterized in that: The microrobot according to any one of claims 1 to 3 further comprises a control unit capable of controlling the motion state of the microrobot.

5. The drug delivery system according to claim 4, wherein: The microrobot has a magnetic structure layer on the outside, and the control unit controls the motion state of the microrobot in a magnetic control manner.

6. A method for preparing a microrobot according to any one of claims 1 to 3, characterized in that: The microrobot is prepared by photolithography using degradable hydrogel.

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