CN116803446A - Microtextured microneedle array for transdermal drug delivery and preparation method thereof - Google Patents
Microtextured microneedle array for transdermal drug delivery and preparation method thereof Download PDFInfo
- Publication number
- CN116803446A CN116803446A CN202310813158.XA CN202310813158A CN116803446A CN 116803446 A CN116803446 A CN 116803446A CN 202310813158 A CN202310813158 A CN 202310813158A CN 116803446 A CN116803446 A CN 116803446A
- Authority
- CN
- China
- Prior art keywords
- micro
- microneedle
- microneedle array
- texture
- plane
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title abstract description 5
- 238000013271 transdermal drug delivery Methods 0.000 title abstract description 4
- 238000012545 processing Methods 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 12
- 150000002500 ions Chemical class 0.000 claims description 3
- 229910021421 monocrystalline silicon Inorganic materials 0.000 claims description 3
- 230000037317 transdermal delivery Effects 0.000 claims description 3
- 239000011159 matrix material Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 28
- 229940079593 drug Drugs 0.000 abstract description 13
- 210000003491 skin Anatomy 0.000 abstract description 6
- 210000002615 epidermis Anatomy 0.000 abstract description 5
- 230000008569 process Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000003491 array Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000010884 ion-beam technique Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 238000012449 Kunming mouse Methods 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000001659 ion-beam spectroscopy Methods 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000002210 silicon-based material Substances 0.000 description 1
- 230000008591 skin barrier function Effects 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000013077 target material Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Landscapes
- Media Introduction/Drainage Providing Device (AREA)
Abstract
The invention discloses a microtextured microneedle array for transdermal drug delivery and a preparation method thereof, wherein each microneedle is in a pyramid shape, and the top of each microneedle is a plane; at least one side surface of the microneedle is provided with a micro-texture, the micro-texture is a groove body structure, and the included angle between the axis of the groove body and the plane of the bottom of the microneedle is 20-90 degrees. The micro-texture microneedle array is used for puncturing skin to transport medicines, and can transport medicine solution into the epidermis layer, so that painless, micro-traumatic, efficient and targeted treatment is realized.
Description
Technical Field
The invention relates to the technical field of micro-nano processing, and particularly provides a monocrystalline silicon material micro-texture microneedle array based on a FIB technology and a preparation method thereof.
Background
The statements herein merely provide background information related to the present disclosure and may not necessarily constitute prior art.
Microneedle therapy can accelerate drug delivery through the stratum corneum and microneedle arrays can enhance transdermal delivery as a method of temporarily destroying skin barrier function. Microneedle arrays are composed of a plurality of microneedles distributed in an array at a fixed pitch, typically 25 μm to 2000 μm in height, and are divided into different shapes and constituent materials (e.g., silicon, metals, saccharides, and biodegradable polymers). Microneedles for transdermal administration have been used to detect and treat a number of diseases, in addition to skin cancer, also infections, diabetes, obesity and eye diseases.
Microneedle administration has no advantage over oral administration and parenteral routes: (1) Can be applied to small-molecule and large-molecule medicines, and has low requirement on molecular size. (2) The active pharmaceutical ingredient is painless in use, does not destroy nerve endings, is more acceptable, and eliminates fear generated by administration of hypodermic needles. (3) The first pass effect of liver and the inactivating effect of gastrointestinal tract are avoided, and the drug efficacy is enhanced, so that the dosage of drug delivery can be reduced. (4) Compared with a hypodermic needle, the microbial permeability of the microneedle administration is low, the amount of penetration of the epidermis by the microneedle is small, and the epidermis at the injection site heals quickly. (5) Delivery of the drug targeted for a particular skin area may be achieved.
However, the surface of the micro needle in the existing micro needle array is smooth, the drug loading is small, certain specific requirements are difficult to meet by one-time administration, psychological burden of patients can be caused by multiple administrations, and drug waste is easy to cause.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a micro-texture microneedle array for transdermal drug delivery and a preparation method thereof. The micro-texture microneedle array is used for puncturing skin to transport medicines, and can transport medicine solution into the epidermis layer, so that painless, micro-traumatic, efficient and targeted treatment is realized.
In order to achieve the above object, the present invention is realized by the following technical scheme:
in a first aspect, the present invention provides an array of microtextured microneedles for transdermal delivery, each microneedle being pyramid-shaped with a planar top; at least one side surface of the microneedle is provided with a micro-texture, the micro-texture is a groove body structure, and the included angle between the axis of the groove body and the plane of the bottom of the microneedle is 20-90 degrees.
The microtexture of the tank body structure provides space for holding liquid medicine, and is convenient for the medicine to remain before delivery. The included angle between the axis of the groove body and the plane of the bottom of the micro needle is 20-90 degrees, so that the micro-texture processing is convenient, and when the micro needle array is horizontally placed, the opening of the micro-texture faces obliquely upwards, the medicine carrying of the medicine is convenient, and the medicine waste is effectively prevented.
The top of the micro needle is provided with a plane so as to avoid the breakage of the needle tip.
In some embodiments, the matrix material of the microneedle array is monocrystalline silicon.
In some embodiments, each microneedle is quadrangular, with a microneedle height of 150-250 μm.
Preferably, the opposite sides of the rectangular pyramid are processed with microtexture. The method aims to reduce the cross intercommunication of the grooves in the needle body so as to improve the integral strength of the micro needle.
Further preferably, the number of microtextures per side is 2-4, arranged along the top of the microneedle towards the bottom of the microneedle.
Still more preferably, the microtexture increases in size along the top of the microneedle toward the bottom of the microneedle.
Still more preferably, the microtexture is 15-25 μm wide, 25-60 μm long and 30-120 μm deep.
Preferably, on the same side, the distance between two adjacent microtextures is 4-10 μm.
In some embodiments, the area of the microneedle top plane is 20-50 μm 2 。
In some embodiments, the axis of the microtextured grooves is at an angle of 30-60 ° to the microneedle bottom plane.
In a second aspect, the present invention provides a method of preparing a microtextured microneedle array for transdermal administration, comprising the steps of:
processing a plane on top of the microneedles in the microneedle array;
the incidence angle of FIB ions is adjusted to be 20-90 degrees with the plane of the bottom of the micro-needle, and micro-textures are processed from top to bottom on the side surface of the micro-needle;
the technological parameters of the FIB are 20-40keV and 50-70nA.
FIB processing of microneedle arrays relies on ion beam sputtering. According to different processing targets, 3-5 workpiece atoms can be removed from each incident Ga ion, and the material removal amount can be accurately controlled. The focused ion beam sputter milling process can process materials of greater hardness, including cemented carbide, single crystal diamond, and the like. Compared with the precise grinding technology, the FIB processing micro-texture process has no mechanical force effect, reduces the occurrence of damage condition, and prepares the micro-needle surface texture with nanometer characteristic dimension finer.
The beneficial effects achieved by one or more embodiments of the present invention described above are as follows:
the micro-texture processed by the FIB technology has high precision, good surface integrity and small damage to the target material. The stress generated by the puncture of the micro-texture microneedle array prepared by the method is far greater than the limit stress of silicon, enough space is provided for accommodating the medicament, the medicament can be accurately released into the epidermis layer after the skin is punctured by the micro-texture microneedle array, accurate medicament administration is realized, a medicament puncture experiment is carried out, the coverage area of the micro-texture microneedle array for retaining the medicament on the skin is greater than that of a common microneedle, and the medicament carrying effect of the micro-texture microneedle array is superior to that of the common microneedle array.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention.
FIG. 1 is a flow chart of FIB-processed microtexture;
FIG. 2 is a microneedle array prior to FIB processing of a microtexture;
FIG. 3 is a microtexture of various processing steps of the microtexture;
fig. 4 is a graph comparing drug loading of different microneedles in the examples, a is the drug loading of the microneedles without the microtexture, and b is the drug loading of the 45 ° process microtexture microneedles.
Detailed Description
It should be noted that the following detailed description is illustrative and is intended to provide further explanation of the invention. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
The invention is further illustrated below with reference to examples.
Example 1
The embodiment specifically comprises the following steps:
(1) The micro-texture processing process is shown in fig. 1, wherein the substrate is a complete pyramid, a plane is processed at the top of the pyramid in the first step, the micro-texture is processed at a fixed angle on the inclined plane in the second step, the ion beam processing is performed on the inclined plane in the process shown in the figure (c), the angle is selected by inclining the horizontal plane of the top of the micro-needle by 30 degrees, and finally the micro-needle shown in the figure (d) is prepared by processing the same structure on the opposite side. The final micro-texture microneedle is in a pyramid-shaped structure, a plane is reserved at the top of the final micro-texture microneedle so as to prevent the needlepoint from breaking, the two opposite side surfaces of the final micro-texture microneedle have the same structure, and rectangular micro-textures with gradually enlarged sizes are distributed from top to bottom. The microtexture on the second microneedle was processed in the same manner with the 30 ° horizontal tilt replaced with 45 °.
(2) The microtextured dimensions are shown in Table 1, with the bevels being processed at 45 and 30 horizontal inclinations, respectively. The three micro-textures on the inclined plane are different in size, the micro-texture interval is 5 mu m, the length is increased from top to bottom, the lengths of the 30-degree horizontal dip angle processing micro-textures are 30 mu m, 42 mu m and 56 mu m in sequence, and the lengths of the 45-degree horizontal dip angle processing micro-textures are 30 mu m, 44 mu m and 56 mu m in sequence. The design is to keep the edge of the micro-texture at a certain distance from the pyramid edge and to increase the medicine carrying capacity as much as possible. The middle and bottom microtexture remain unchanged in width, increasing in sequence length and depth, and the design takes the same goal.
(3) The micro-texture is processed according to the flow of the previous section, and the effects of each stage are shown in fig. 3, wherein (a), (c) and (e) are sequences for processing the micro-texture with the horizontal inclination angle of 45 degrees, and (b), (d) and (f) are sequences for processing the micro-texture with the horizontal inclination angle of 30 degrees. The FIB equipment processes and selects 30keV and 60nA parameters. The figure shows that the grooves sputtered by the FIB in each link are smooth in wall adhesion, complete in rectangular morphology, and have enough space for accommodating the drug solution, and each item meets the requirements.
(4) The KM mice with 1-7 days are used as experimental materials, the hair of the mice does not grow out at the week age, the skin is smooth and atraumatic, the influence of the hair is removed, and the observation effect is good. The different microtextured microneedles are used as variables for analysis, and the dyeing results are different, as shown in fig. 4, wherein a is the drug carrying capacity of the microneedles without microtexture, b is the drug carrying capacity of the microneedles with the microtexture processed at 45 degrees, and the quantity and the arrangement of the microneedles with the microtexture are the same, and the difference is that only one microtexture is processed, the processing parameters of the microtexture are shown in table 1, and the other microtexture is not processed. The calculated area shows that the area of the dyed area of the micro-texture microneedle is larger than that of the common microneedle, namely the micro-texture microneedle carries more medicine.
TABLE 1
The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A microtextured microneedle array for transdermal administration, comprising: each microneedle is in a pyramid shape, and the top of each microneedle is a plane; at least one side surface of the microneedle is provided with a micro-texture, the micro-texture is a groove body structure, and the included angle between the axis of the groove body and the plane of the bottom of the microneedle is 20-90 degrees.
2. The micro-textured microneedle array for transdermal administration of claim 1, wherein: the matrix material of the microneedle array is monocrystalline silicon.
3. The micro-textured microneedle array for transdermal administration of claim 2, wherein: each microneedle has a quadrangular pyramid shape, and the height of the microneedle is 150-250 μm.
4. A microtextured microneedle array for transdermal administration according to claim 3, characterized in that: the opposite sides of the rectangular pyramid are machined with micro-textures.
5. The micro-textured microneedle array for transdermal administration of claim 4, wherein: the number of the micro-textures of each side surface is 2-4, and the micro-textures are arranged along the top of the micro-needle to the bottom of the micro-needle;
preferably, the microtexture increases in size along the top of the microneedle toward the bottom of the microneedle.
6. The micro-textured microneedle array for transdermal administration of claim 1, wherein: the micro-texture has a width of 15-25 μm, a length of 25-60 μm, and a depth of 30-120 μm.
7. The micro-textured microneedle array for transdermal administration of claim 1, wherein: on the same side, the distance between two adjacent micro-textures is 4-10 μm.
8. The micro-textured microneedle array for transdermal administration of claim 1, wherein: the area of the top plane of the microneedle is 20-50 μm 2 。
9. The micro-textured microneedle array for transdermal administration of claim 1, wherein: the included angle between the axis of the micro-texture groove body and the plane of the bottom of the micro-needle is 30-60 degrees.
10. A method of preparing a microtextured microneedle array for transdermal delivery, comprising: the method comprises the following steps:
processing a plane on top of the microneedles in the microneedle array;
the incidence angle of FIB ions is adjusted to be 20-90 degrees with the plane of the bottom of the micro-needle, and micro-textures are processed from top to bottom on the side surface of the micro-needle;
the technological parameters of the FIB are 20-40keV and 50-70nA.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310813158.XA CN116803446A (en) | 2023-07-04 | 2023-07-04 | Microtextured microneedle array for transdermal drug delivery and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310813158.XA CN116803446A (en) | 2023-07-04 | 2023-07-04 | Microtextured microneedle array for transdermal drug delivery and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116803446A true CN116803446A (en) | 2023-09-26 |
Family
ID=88080676
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310813158.XA Pending CN116803446A (en) | 2023-07-04 | 2023-07-04 | Microtextured microneedle array for transdermal drug delivery and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116803446A (en) |
-
2023
- 2023-07-04 CN CN202310813158.XA patent/CN116803446A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101634836B1 (en) | Microneedle device | |
| US5792110A (en) | Systems and methods for delivering therapeutic agents to selected sites in a subject | |
| US10737081B2 (en) | Painless and patchless shooting microstructure | |
| US9011392B2 (en) | Methods and devices for delivering agents across biological barriers | |
| EP1517722B1 (en) | Method of coating transdermal drug delivery devices having coated microprotrusions | |
| CN101432040A (en) | Microprojection array application with sculptured microprojections for high drug loading | |
| KR20060097751A (en) | Apparatus and method for enhancing transdermal drug delivery | |
| CN1863572A (en) | Method and device for enhancing transdermal agent flux | |
| CN105982842B (en) | Microneedle preparation and method for producing microneedle preparation | |
| JP2007519613A (en) | Stabilized DNA composition for coating microprojections | |
| Xue et al. | Drug-eluting microneedles for self-administered treatment of keloids | |
| KR102367746B1 (en) | Method of manufacturing micro needle transdermal drug patch and ultrasonic delivery device thereof | |
| US20210121674A1 (en) | Japanese encephalitis vaccine-containing microneedle array | |
| CN116803446A (en) | Microtextured microneedle array for transdermal drug delivery and preparation method thereof | |
| Babu et al. | Unravelling the role of microneedles in drug delivery: Principle, perspectives, and practices | |
| CN209751939U (en) | Microneedle structure with uniformly distributed and introduced drugs | |
| US11738185B2 (en) | In-plane metal microneedle array and manufacturing method therefor | |
| EP3701997B1 (en) | High-density microneedle | |
| EP3991778A1 (en) | Microneedle array having uneven needle density | |
| KR20190028180A (en) | Microneedle template, and microneedle manufactured by using the same | |
| KR101947624B1 (en) | Multi type micro-needle | |
| Arora et al. | Microneedles: Recent advances and development in the field of transdermal drug delivery technology | |
| JP4985025B2 (en) | Microneedle chip assembly, microneedle chip, medical instrument, microneedle chip assembly manufacturing method, and microneedle chip manufacturing method | |
| CN110270006A (en) | Prismatic metal micro-needle and preparation method thereof | |
| WO2024097385A1 (en) | Microneedle array applicator and system |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |