Microneedle with porous surface as well as preparation method and application of microneedle
By forming a porous structure on the surface of the microneedle, the existing microneedle detection sensitivity is solved, and higher signal molecule acquisition efficiency and detection sensitivity are achieved.
Patent Information
- Application Number
- CN202411958185.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-27
- Publication Date
- 2025-04-11
AI Technical Summary
During the detection of the existing microneedles, due to the smooth surface and limited specific surface area, the adsorption and enrichment efficiency of the target molecules is low and the detection sensitivity is insufficient.
The gelatin particles are added by mixing methacrylylated gelatin with a photoinitiator, and microneedles with surface porous structures are formed by centrifugal dispersion and ultraviolet crosslinking.
It improves the specific surface area and adsorption sites of microneedles, significantly improves the acquisition and detection sensitivity of signal molecules, and has important application value in the fields of biomolecular detection and drug adsorption enrichment.
Smart Images
Figure CN119798572A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of biomaterials, and particularly relates to a surface porous microneedle and a preparation method and application thereof. Background Art
[0002] As a cutting-edge micro-biomaterial and detection tool, microneedles have been widely used in drug delivery, vaccination, wound healing, and biological detection due to their low invasiveness, simple operation, and wide range of applications. In biological detection, microneedles, as a medium for collecting and detecting target molecules, obtain trace biological samples by directly piercing the skin or tissue, showing great application prospects in precision medicine and instant detection. However, in in vivo detection, the concentration of target molecules, especially biomarkers, is usually low, which increases the difficulty of detection to a certain extent. In order to improve the detection sensitivity, it is necessary to effectively enrich the target molecules and enhance the signal to obtain a sufficiently strong detection signal for subsequent analysis.
[0003] In the existing technology, the chemical structure of the material itself is mostly optimized, such as selecting different materials or modifying functional groups. However, such microneedles usually have smooth surfaces and limited specific surface area, and the adsorption and enrichment efficiency of target molecules is low, resulting in insufficient detection sensitivity. In addition, although optimizing materials and structures can improve performance, the lack of efficient and scalable preparation processes will also affect the industrial development of the technology. Summary of the invention
[0004] In order to overcome at least one of the problems existing in the above-mentioned prior art, the present invention provides a surface porous microneedle and a preparation method and application thereof.
[0005] To this end, the present invention adopts the following technical solutions:
[0006] The first aspect of the present invention provides a method for preparing a surface porous microneedle, characterized in that it comprises the following steps:
[0007] 1) adding methacrylated gelatin and a photoinitiator into water and stirring to form a matrix solution;
[0008] 2) adding gelatin particles into the matrix solution to obtain a gelatin solution;
[0009] 3) injecting the gelatin solution into the microneedle mold and centrifugally dispersing it;
[0010] 4) placing the mold under ultraviolet light for cross-linking to form a solid gel structure, demoulding, and soaking the solid gel structure in water to remove the gelatin particles on the surface to obtain the surface porous microneedles.
[0011] In the above preparation method, the gelatin particles in step 2) are obtained by crushing gelatin and sieving.
[0012] In the above preparation method, the centrifugal dispersion in step 3) is used to enrich the gelatin particles on the surface of the microneedles.
[0013] Preferably, in the above step 1), the photoinitiator is a water-based photoinitiator. Further preferably, the photoinitiator is an acylphosphine oxide-based water-based photoinitiator. Even more preferably, the photoinitiator is phenyl (2,4,6-trimethylbenzoyl) phosphate lithium salt.
[0014] Preferably, in the above step 1), the mass ratio of the methacrylated gelatin to the photoinitiator is (10-20):(0.1-0.2). Further preferably, the mass ratio of the methacrylated gelatin to the photoinitiator is (15-20):(0.1-0.2). Even more preferably, the mass ratio of the methacrylated gelatin to the photoinitiator is 20:0.2.
[0015] Preferably, in the above step 2), the mass fraction of the gelatin particles is 0.5 to 1.5. Further preferably, the mass fraction of the gelatin particles is 0.5 to 1.0. Even further preferably, the mass fraction of the gelatin particles is 0.5.
[0016] Preferably, in the above step 3), the speed of the centrifugal dispersion is 4500-5000 rpm, and the time of the centrifugal dispersion is 10-20 min.
[0017] Preferably, in the above step 4), the wavelength of the ultraviolet light is 360-405 nm, and the cross-linking time is 30-60 s.
[0018] The second aspect of the present invention provides a surface porous microneedle prepared according to the method for preparing a surface porous microneedle according to the first aspect of the present invention.
[0019] Preferably, the pores of the surface porous microneedles are not interconnected.
[0020] Preferably, the pore diameter of the surface porous microneedles is 20 to 50 μm.
[0021] The third aspect of the present invention provides an application of a surface porous microneedle for preparing a biological detection material. The surface porous microneedle is prepared by the above preparation method, or is the above surface porous microneedle.
[0022] According to the present invention, there are at least the following beneficial effects:
[0023] 1) Based on the water solubility of gelatin particles, the pore distribution is precisely controlled through photocrosslinking and post-processing steps, and the preparation method is simple and efficient.
[0024] 2) Surface porous microneedles have a larger specific surface area and more adsorption sites due to their surface structure, which effectively improves the collection and detection sensitivity of signal molecules. Surface porous microneedles have important application value in the fields of biological molecule detection, drug adsorption and enrichment, etc., and provide an innovative basis for the further development of new biosensors and precision medical technologies, and have broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS
[0025] The present invention is further described below with reference to the accompanying drawings, embodiments and comparative examples, wherein:
[0026] Figure 1 Schematic diagram of the preparation process of surface porous microneedles.
[0027] Figure 2 This is a scanning electron microscope image of the surface porous microneedle prepared in Example 1.
[0028] Figure 3 This is a scanning electron microscope image of the surface-free microneedle prepared in Comparative Example 1.
[0029] Figure 4 The graph is a graph showing the absorbance of curcumin in the eluate at 425 nm measured for the surface porous microneedles and surface non-porous microneedles prepared in Example 1 and Comparative Example 1. DETAILED DESCRIPTION
[0030] The present invention is further described in detail below through specific examples and comparative examples, but is not limited to all discussions and data.
[0031] Unless otherwise specified, the raw materials, reagents or devices used in the examples and comparative examples can be obtained from conventional commercial sources or by prior art methods. Unless otherwise specified, the experiments or test methods are conventional methods in the art.
[0032] Embodiment 1:
[0033] A method for preparing a surface porous microneedle comprises the following steps:
[0034] 1) Put gelatin into a ball mill and grind it into gelatin powder. Sieve the gelatin powder with a 500-mesh sieve to obtain gelatin particles with uniform particles and a particle size of 20 to 50 μm;
[0035] 2) Weigh 20 g of methacrylated gelatin and 0.2 g of phenyl (2,4,6-trimethylbenzoyl) lithium phosphate and add them to 79.8 g of water, stir to form a matrix solution;
[0036] 3) Add 0.5 g of gelatin particles to the matrix solution and stir gently to obtain a uniformly dispersed gelatin solution;
[0037] 4) Inject the gelatin solution into the silica gel microneedle mold and centrifuge at 5000 rpm for 10 min to allow the gelatin particles to accumulate on the microneedle surface;
[0038] 5) The mold was placed under 405 nm ultraviolet light for 50 seconds to cross-link and form a solid gel structure.
[0039] 6) demoulding, soaking the solid gel structure in water to dissolve the gelatin particles on the surface to obtain surface porous microneedles.
[0040] Comparative Example 1:
[0041] A method for preparing a microneedle with no pores on the surface comprises the following steps:
[0042] 1) Weigh 20 g of methacrylated gelatin and 0.2 g of phenyl (2,4,6-trimethylbenzoyl) lithium phosphate and add them into 79.8 g of water, stir to form a matrix solution;
[0043] 2) injecting the matrix solution into the silicone microneedle mold;
[0044] 3) The mold was placed under 405 nm ultraviolet light for 50 seconds to cross-link and form a solid gel structure.
[0045] 4) Demolding to obtain microneedles with no pores on the surface.
[0046] Test example:
[0047] (1) Figure 1 In the figure, the round particles represent gelatin particles. The gelatin particles are dispersed onto the surface of the microneedle by centrifugation. After the gelatin particles are removed by water elution, surface porous microneedles are obtained.
[0048] (2) The surface porous microneedles prepared in Example 1 were observed at different magnifications using a scanning electron microscope (SEM). The results are as follows: Figure 2 As shown, it can be seen that the pore structure is uniform and controllable, and is mainly distributed on the tip and surface of the microneedle.
[0049] (3) Using a scanning electron microscope (SEM), the surface-free microneedles prepared in Comparative Example 1 were observed at different magnifications. The results are as follows: Figure 3 As shown, the surface of the non-porous microneedles is smooth and has no pores.
[0050] (4) SBF simulated body fluid containing curcumin at a concentration of 0.002 mg / mL was prepared, and the microneedles of Example 1 and Comparative Example 1 of the same size were immersed in the simulated body fluid respectively, and the immersion time was 10 min at 37° C. The microneedles were taken out, and the curcumin adsorbed on the surface of the microneedles was eluted with 95% ethanol, and the eluate was collected. The absorbance of curcumin in the eluate was measured at 425 nm using an ELISA instrument, and the curcumin concentration was calculated according to the standard curve to obtain Figure 4 . After analysis, the absorbance values of the porous surface microneedles of Example 1 and the non-porous surface microneedles of Comparative Example 1 at 425 nm were 0.0854 and 0.0620, respectively, and the difference was statistically significant (p<0.01). The porous surface microneedles of Example 1 have a larger specific surface area and more adsorption sites due to their surface structure, which effectively improves the detection sensitivity of low-concentration curcumin.
Claims
1. A method for preparing a surface porous microneedle, characterized in that: The following steps are involved: 1) adding methacrylated gelatin and a photoinitiator into water and stirring to form a matrix solution; 2) adding gelatin particles into the matrix solution to obtain a gelatin solution; 3) injecting the gelatin solution into the microneedle mold and centrifugally dispersing it; 4) placing the mold under ultraviolet light for cross-linking to form a solid gel structure, demoulding, and soaking the solid gel structure in water to remove the gelatin particles on the surface to obtain the surface porous microneedles.
2. The method for preparing a surface porous microneedle according to claim 1, characterized in that: In step 1), the photoinitiator is a water-based photoinitiator.
3. The method for preparing a surface porous microneedle according to claim 1, characterized in that: In step 1), the mass ratio of the methacrylated gelatin to the photoinitiator is (10-20): (0.1-0.2).
4. The method for preparing a surface porous microneedle according to claim 1, characterized in that: In step 2), the mass fraction of the gelatin particles is 0.5 to 1.
5.
5. The method for preparing a surface porous microneedle according to claim 1, characterized in that: In step 3), the speed of the centrifugal dispersion is 4500-5000 rpm, and the time of the centrifugal dispersion is 10-20 min.
6. The method for preparing a surface porous microneedle according to claim 1, characterized in that: In step 4), the wavelength of the ultraviolet light is 360 to 405 nm, and the cross-linking time is 30 to 60 seconds.
7. A surface porous microneedle, characterized in that: The surface porous microneedle is prepared by the preparation method of the surface porous microneedle according to any one of claims 1 to 6.
8. The surface porous microneedle according to claim 7, characterized in that: The pores of the surface porous microneedles are not interconnected.
9. The surface porous microneedle according to claim 7, characterized in that: The pore diameter of the surface porous microneedle is 20-50 μm.
10. Application of a surface porous microneedle in the preparation of biological detection materials, characterized in that: The surface porous microneedle is prepared by the preparation method of the surface porous microneedle according to any one of claims 1 to 6, or is the surface porous microneedle according to any one of claims 7 to 9.