KR101221192B1 - Microneedle array and manufacturing method thereof - Google Patents
Microneedle array and manufacturing method thereof Download PDFInfo
- Publication number
- KR101221192B1 KR101221192B1 KR1020100095980A KR20100095980A KR101221192B1 KR 101221192 B1 KR101221192 B1 KR 101221192B1 KR 1020100095980 A KR1020100095980 A KR 1020100095980A KR 20100095980 A KR20100095980 A KR 20100095980A KR 101221192 B1 KR101221192 B1 KR 101221192B1
- Authority
- KR
- South Korea
- Prior art keywords
- microneedle array
- nanoparticles
- microneedle
- mold
- manufacturing
- Prior art date
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0023—Drug applicators using microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0053—Methods for producing microneedles
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Medical Informatics (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Media Introduction/Drainage Providing Device (AREA)
Abstract
The present invention relates to a method for manufacturing a polymeric microneedle array coated with nanoparticles, specifically 1) preparing a microneedle array template; 2) coating nanoparticles into the microneedle array template; 3) injecting a biodegradable polymer into the nanoneedle-coated microneedle array template; 4) It provides a method of manufacturing a microneedle array comprising the step of separating the microneedle array from the microneedle array template into which the nanoparticles and biodegradable polymer are injected.
Description
The present invention relates to a polymeric microneedle array coated with nanoparticles and a method of manufacturing the same.
In general, needles, which are directly injected subcutaneously, which is one of drug delivery methods, have the disadvantage that they may cause pain and cause inflammation. In addition, bleeding occurs, depending on the age and characteristics may be difficult to injection. Various microneedles have been manufactured to overcome these disadvantages.
The microneedle has the greatest advantage of minimizing pain and can minimize bleeding or inflammatory reactions. In addition, since the local injection of the drug is possible, we have been actively researched because there is an advantage that it can be effectively and continuously added only to the desired site for injection.
Conventional microneedles have often been manufactured using a metal material or a silicon wafer so that the needles made of microunits can have adequate robustness. However, due to the size of the microneedle, if it is injected into the human body, it breaks when a certain amount of force is applied, and the broken needle can be inserted into the human body and affect other organs. Can come. For this reason, there is a problem in that it is difficult to use the general public, and if a specialist performs the procedure, it becomes troublesome to go through the verification process after the procedure.
Due to the above problems, in recent years, many attempts have been made to produce microneedles using biodegradable materials that are harmless to the human body. Microneedles were manufactured using maltose in the form of powder, which is a natural sugar. Due to the nature of the manufacturing process, the drug and maltose to be injected are mixed and subjected to high temperature treatment. However, the drug that can be used is limited, there is a problem that the microneedle array must be manufactured using only a drug that can withstand high temperatures. In addition, there is an advantage of being made of a material harmless to the human body, but there is a disadvantage that its application capacity is greatly reduced because it can not use a wide variety of drugs.
Therefore, the present inventors have studied the manufacturing method of the microneedle array, as a result of manufacturing a nanoparticle-coated polymer microneedle array can be manufactured in an environmentally friendly and simple process at a lower cost than the conventional technology, and made of polystyrene and iron oxide It was confirmed that the nanoparticles can be delivered safely and effectively through the skin and completed the present invention.
The present invention is to provide a nanoparticle-coated polymeric microneedle array and a method of manufacturing the same, can be produced in a low cost environmentally friendly and simple process, and the nanoparticles such as pharmaceuticals, biological drugs such as DNA, RNA, protein, etc. It is to provide a manufacturing method that can be safely and effectively delivered to a desired site in vivo by combining various materials.
In accordance with one aspect of the present invention, a method of manufacturing a microneedle array includes the steps of: 1) manufacturing a microneedle array mold; 2) coating nanoparticles into the microneedle array template; 3) injecting a biodegradable polymer into the nanoneedle-coated microneedle array template; 4) It provides a method of manufacturing a microneedle array comprising the step of separating the microneedle array from the microneedle array template into which the nanoparticles and biodegradable polymer are injected.
As used herein, the term "microneedle" refers to a special microstructure associated with an array capable of penetrating the stratum corneum to facilitate transdermal delivery of therapeutic agents through the skin or sampling of fluid. By way of example, the microstructures may include needles or needle like structures and other structures capable of penetrating the stratum corneum.
The term "array" as used herein also means a medical device comprising one or more structures capable of penetrating the stratum corneum to facilitate transdermal delivery of the therapeutic agent or sampling of the fluid through or into the skin.
In the present invention, the nanoparticles are preferably polystyrene or iron oxide, and the size of the nanoparticles of polystyrene and iron oxide is 50 mm, in which rhodamine having red fluorescence is dyed. use.
In the present invention, the biodegradable polymer may be a carboxy methyl cellulose (CMC) or agarose mixture. The CMC is well known as a polymer material and has a property of expanding and viscous when mixed with water. CMC is a biodegradable material that is widely used in food, medicine, cosmetics, etc., and is suitable for use as a raw material of microneedle array because of its high polymer and safety for human body.It has a higher melting point than agarose. There is an advantage that can be produced. In addition, the agarose is well known as a constituent of agar, has the property of absorbing water and expands, and the hardness is increased when a sugar such as sucrose (D (+)-sucrose) is mixed Based on this principle, to increase the hardness of the microneedle array An agarose mixture mixed with sucrose is used.
Step 1) in the present invention refers to the step of manufacturing a microneedle array template.
Specifically, in step 1), the mold of the microneedle array is manufactured by etching a template plate of PDMS material using a laser writer.
By performing the above process, grooves having a constant arrangement and length are formed in the mold plate, and the grooves can be manufactured by inserting raw materials into the grooves. The etching uses a prefabricated drawing, which can be variously designed. In addition, the drawing design can adjust the number of needles, the interval of arrangement through the program and the length by adjusting the power of the laser.
In the present invention, step 2) means coating the nanoparticles on the microneedle array template.
Specifically, step 2) is performed by injecting polystyrene or iron oxide nanoparticles into the microneedle array mold, and then coating by centrifuge.
The centrifuge is carried out at a speed of 2000rpm or more. In addition, the centrifuge is performed by stirring for 5 minutes. At this time, since the nanoparticles are in a water-soluble state and difficult to enter the ends of the microneedle array molds, the nanoparticles can enter the hole ends of the molds well by the centrifuge (FIGS. 2, 5, and 7).
In the present invention, step 3) means injecting a biodegradable polymer into the microneedle array template coated with the nanoparticles.
Specifically, step 3) is carried out by injecting a mixture of CMC or agarose in the microneedle template coated with nanoparticles and then inserted into a centrifuge.
The centrifuge is carried out at a speed of 2000rpm or more. In addition, the centrifuge is performed by stirring for 5 minutes. At this time, since the CMC or agarose mixture is semi-solid, it is difficult to enter the end of the microneedle array mold, so that the CMC or agarose mixture can enter the hole end of the mold by a centrifuge.
In addition, the microneedle array in the mold is still semi-solid, so it is difficult to serve as a needle because of its low rigidity. The melting point of the agarose is 60 ℃, and when the agarose mixture is heated at 60 ℃ or more, the microneedle array is melted again, the heat must be continuously applied below 60 ℃ to make a solid solid state. The CMC heats the mold filled with the raw material at a temperature of 82 ° C. or more for 1 hour or more, so that the CMC is dried and remains in a hard form. By carrying out this process, the microneedle array, which has been fully shaped from semi-solid to solid, can be easily separated from the mold and less damage to the needle occurs.
In the present invention, the step 4) means separating the microneedle array from the microneedle array template into which the nanoparticles and the biodegradable polymer are injected.
Specifically, step 4) may dry the microneedle array template in which the nanoparticles and the biodegradable polymer are injected to separate the microneedle array to obtain a nanoneedle coated microneedle array.
In addition, when the fabricated microneedle array is inserted into the skin, a constant pressure must be continuously applied to the micropores of the skin so that the nanoparticles can be easily delivered.
Microneedle array according to the present invention can be produced in a low cost environmentally friendly and simple process, it is possible to produce a needle with high stability using a biodegradable polymer. In addition, the microneedle array of the present invention can be safely and effectively delivered to the desired site in vivo by combining a variety of substances, such as drugs, biological drugs such as DNA, RNA, protein to the nanoparticles. Furthermore, the microneedle array of the present invention can solve the disadvantages of the conventional nanoparticle delivery method by coating the nanoparticles and can be widely used for medical or cosmetic purposes because it can be locally injected, it is stable when applied to the skin It can also be used as a cosmetic or medical patch for drug delivery.
1 shows a side view of a completed mold according to one embodiment of the present invention.
Figure 2 shows a method of injecting nanoparticles in a mold according to an embodiment of the present invention.
Figure 3 shows a method of injecting the raw material into the mold according to an embodiment of the present invention.
Figure 4 shows a planar optical photo and fluorescence photograph with the nanoparticles inserted in the mold.
5 (a) and 5 (b) show a cross-sectional optical photograph and a fluorescence photograph introduced into the mold inner surface of the nanoparticles to which the fluorescent dye is bound.
6 (a) and 6 (b) show microneedle optical and fluorescent photographs coated with nanoparticles having fluorescent dyes bonded thereto.
Figure 7 shows an optical photograph of the microneedle made by adding a sugar to agarose and CMC according to an embodiment of the present invention.
8 shows a state in which a microneedle array is removed from a mold according to an embodiment of the present invention.
Figure 9 (a), (b) shows a scanning electron microscope (SEM) photograph of the microneedle array according to an embodiment of the present invention.
10 (a) and 10 (b) show optical and fluorescent photographs in which nanoparticles are introduced by applying to porcine skin according to an embodiment of the present invention.
Hereinafter, preferred embodiments of the present invention will be presented to assist in understanding the present invention. However, the following examples are merely provided to more easily understand the present invention, and the contents of the present invention are not limited by the examples.
Manufacturing example : Microneedle Array mold ( mold ) Produce
The mold was cured by mixing Sylgard 184A and DC 184A in a constant ratio to completely remove the bubbles and drying them in a 70 ℃ oven. The cured mold was etched on the surface using a laser lighter (PL-40K, Korea stamp, Korea) and washed to prepare a microneedle array mold, and a side view of the completed mold is shown in FIG. 1.
Example One : Microneedle Coating polystyrene or iron oxide nanoparticles on the array mold
Polystyrene or iron oxide nanoparticles having rhodamine-stained red fluorescence in the microneedle array mold prepared in the preparation example were coated with a centrifuge at a speed of 2000 rpm or more for 5 minutes, and the nanoparticles were coated on the mold. Is shown in FIG. 2.
Example 2: nanoparticles coated Microneedle Is a biodegradable polymer agarose Injecting the mixture
Sucrose (D (+)-sucrose) and the ratio of distilled water 70: 100 in a polyneedle array coated with polystyrene or iron oxide nanoparticles prepared in Example 1 was heated to 20 ~ 30 ℃ and then agarose The agarose mixture prepared by adding and heating again was injected by stirring for 5 minutes at a speed of 2000 rpm or more by a centrifuge, and the method of coating the agarose mixture on the mold is shown in FIG. 3.
Example 3: nanoparticles coated Microneedle Is a biodegradable polymer CMC Injecting
To the microneedle array coated with the polystyrene or iron oxide nanoparticles prepared in Example 1, CMC mixed with distilled water and a mixing ratio of 5% was injected by centrifugation at a speed of 2000 rpm or more for 5 minutes, and the CMC was molded. The method of coating on is shown in FIG.
Example 4: nanoparticles and biodegradable polymers agarose The mixture is injected Microneedle From array mold Microneedle Steps to Detach the Array
The microneedle array mold into which the nanoparticles and agarose mixtures prepared in Example 2 were injected was dried by heating to below 60 ° C., and the microneedle arrays were separated to prepare nanoneedle coated microneedle arrays. Is shown in FIG. 8.
Example 5: nanoparticles and biodegradable polymers CMC Injected Microneedle From array mold Microneedle Steps to Detach the Array
After the nanoparticles prepared in Example 3 and the CMC-injected microneedle array template were dried by heating at a temperature of 82 ° C. or more for 1 hour or more, the microneedle array was separated to prepare a nanoneedle coated microneedle array. The obtained result is shown in FIG.
Experimental Example 1: Fluorescence Microscope Analysis
In order to determine the surface shape and microstructure of the microneedle arrays prepared in Examples 2, 3, 4, and 5, a fluorescence microscope was analyzed, and the obtained results are shown in FIGS. 4 to 7 and 10. .
4 is a planar optical photograph and a fluorescent photograph in which nanoparticles are inserted into a mold, and FIGS. 5 (a) and 5 (b) are cross-sectional optical photographs and fluorescent photographs introduced into an inner surface of a mold of a fluorescent dye-bound nanoparticle, 6 (a) and 6 (b) are microneedle optical and fluorescent photographs coated with nanoparticles having fluorescent dyes bonded thereto. 4 to 6, it was confirmed that the nanoparticles are well coated on the tip and the surface of the microneedle. 7 is an optical photograph of the microneedle made by adding sugar to agarose and CMC, it was confirmed that the agarose and the CMC was well inserted at the end of the microneedle using a centrifuge, Figure 10 (a), (b) is an optical photo and a fluorescence photograph in which the nanoparticles were applied to the pig skin and confirmed that the nanoparticles were well transferred to the pig skin.
Experimental Example 2: scanning electron microscope analysis
In order to determine the surface shape and microstructure of the microneedle arrays prepared in Examples 4 and 5, the results were analyzed by scanning electron microscopy (SEM), and the obtained results are shown in FIG. 9.
9 (a) and 9 (b) show that the microneedle array is well separated from the microneedle array template by SEM images of the microneedle array.
Claims (10)
2) injecting nanoparticles into the microneedle array template, and then coating the nanoparticles on the microneedle array template with a centrifuge;
3) injecting a biodegradable polymer into the microneedle array template coated with the nanoparticles by a centrifuge;
4) A method of manufacturing a microneedle array coated with nanoparticles on a microneedle, comprising separating the microneedle array from the microneedle array mold into which the nanoparticles and the biodegradable polymer are injected.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020100095980A KR101221192B1 (en) | 2010-10-01 | 2010-10-01 | Microneedle array and manufacturing method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020100095980A KR101221192B1 (en) | 2010-10-01 | 2010-10-01 | Microneedle array and manufacturing method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20120034427A KR20120034427A (en) | 2012-04-12 |
| KR101221192B1 true KR101221192B1 (en) | 2013-01-10 |
Family
ID=46136804
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020100095980A KR101221192B1 (en) | 2010-10-01 | 2010-10-01 | Microneedle array and manufacturing method thereof |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR101221192B1 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103800998A (en) * | 2014-02-24 | 2014-05-21 | 苏州大学 | Silk fibroin gel microneedle system and manufacturing method thereof |
| KR101605963B1 (en) | 2014-09-16 | 2016-03-24 | 포항공과대학교 산학협력단 | micro-needle and sensor for detecting nitrogen monooxide comprising the same |
| KR20170077809A (en) * | 2015-12-28 | 2017-07-06 | 주식회사 엔도더마 | Microstructure for Transdermal Absorption and Process for Preparing the Same |
| CN109562079A (en) * | 2016-08-01 | 2019-04-02 | 釜山大学校产学协力团 | Microneedle patch and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080269685A1 (en) | 2007-04-16 | 2008-10-30 | Parminder Singh | Solvent-cast microneedle arrays containing active |
| US20080312610A1 (en) * | 2005-07-25 | 2008-12-18 | Peter Nicholas Binks | Microarray Device |
| JP2009507573A (en) | 2005-09-06 | 2009-02-26 | セラジェクト， インコーポレイテッド | Solid solution punch comprising drug particles and / or particles adsorbed with drugs |
-
2010
- 2010-10-01 KR KR1020100095980A patent/KR101221192B1/en active IP Right Grant
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080312610A1 (en) * | 2005-07-25 | 2008-12-18 | Peter Nicholas Binks | Microarray Device |
| JP2009507573A (en) | 2005-09-06 | 2009-02-26 | セラジェクト， インコーポレイテッド | Solid solution punch comprising drug particles and / or particles adsorbed with drugs |
| US20080269685A1 (en) | 2007-04-16 | 2008-10-30 | Parminder Singh | Solvent-cast microneedle arrays containing active |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103800998A (en) * | 2014-02-24 | 2014-05-21 | 苏州大学 | Silk fibroin gel microneedle system and manufacturing method thereof |
| KR101605963B1 (en) | 2014-09-16 | 2016-03-24 | 포항공과대학교 산학협력단 | micro-needle and sensor for detecting nitrogen monooxide comprising the same |
| KR20170077809A (en) * | 2015-12-28 | 2017-07-06 | 주식회사 엔도더마 | Microstructure for Transdermal Absorption and Process for Preparing the Same |
| KR102064503B1 (en) | 2015-12-28 | 2020-03-02 | 주식회사 엔도더마 | Microstructure for Transdermal Absorption and Process for Preparing the Same |
| CN109562079A (en) * | 2016-08-01 | 2019-04-02 | 釜山大学校产学协力团 | Microneedle patch and preparation method thereof |
| JP2019527581A (en) * | 2016-08-01 | 2019-10-03 | プサン ナショナル ユニバーシティ インダストリー−ユニバーシティ コーポレーション ファウンデーション | Microneedle patch and manufacturing method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20120034427A (en) | 2012-04-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Gao et al. | Highly porous silk fibroin scaffold packed in PEGDA/sucrose microneedles for controllable transdermal drug delivery | |
| Cahill et al. | Metallic microneedles with interconnected porosity: A scalable platform for biosensing and drug delivery | |
| Zhang et al. | Fabrication, evaluation and applications of dissolving microneedles | |
| Bao et al. | Recent advances in porous microneedles: Materials, fabrication, and transdermal applications | |
| Yang et al. | Recent advances of microneedles used towards stimuli-responsive drug delivery, disease theranostics, and bioinspired applications | |
| Zhu et al. | Rapidly separating microneedles for transdermal drug delivery | |
| Lau et al. | Multilayered pyramidal dissolving microneedle patches with flexible pedestals for improving effective drug delivery | |
| Wang et al. | A fabrication method of microneedle molds with controlled microstructures | |
| JP5863824B2 (en) | Manufacturing method of microstructure | |
| Ye et al. | Fabrication of tip-hollow and tip-dissolvable microneedle arrays for transdermal drug delivery | |
| Liu et al. | Fabrication of dissolving microneedles with thermal-responsive coating for NIR-triggered transdermal delivery of metformin on diabetic rats | |
| Lee et al. | Rapid and repeatable fabrication of high A/R silk fibroin microneedles using thermally-drawn micromolds | |
| Liu et al. | Transdermal delivery of relatively high molecular weight drugs using novel self-dissolving microneedle arrays fabricated from hyaluronic acid and their characteristics and safety after application to the skin | |
| US8043250B2 (en) | High-aspect-ratio microdevices and methods for transdermal delivery and sampling of active substances | |
| Chen et al. | Rapidly fabricated microneedle arrays using magnetorheological drawing lithography for transdermal drug delivery | |
| Gao et al. | PEGDA/PVP microneedles with tailorable matrix constitutions for controllable transdermal drug delivery | |
| Anjani et al. | Elucidating the impact of surfactants on the performance of dissolving microneedle array patches | |
| Zhuang et al. | Study on the fabrication and characterization of tip-loaded dissolving microneedles for transdermal drug delivery | |
| KR101221192B1 (en) | Microneedle array and manufacturing method thereof | |
| Wu et al. | Challenges and strategies in developing microneedle patches for transdermal delivery of protein and peptide therapeutics | |
| Qiao et al. | A sample and detection microneedle patch for psoriasis MicroRNA biomarker analysis in interstitial fluid | |
| Koyani | Synthetic polymers for microneedle synthesis: from then to now | |
| Loh et al. | Design and fabrication of customizable microneedles enabled by 3D printing for biomedical applications | |
| Rai et al. | Microneedle arrays for cutaneous and transcutaneous drug delivery, disease diagnosis, and cosmetic aid | |
| Iliescu et al. | A review on transdermal drug delivery using microneedles: Current research and perspective |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| AMND | Amendment | ||
| E601 | Decision to refuse application | ||
| AMND | Amendment | ||
| X701 | Decision to grant (after re-examination) | ||
| GRNT | Written decision to grant | ||
| FPAY | Annual fee payment |
Payment date: 20160107 Year of fee payment: 4 |
|
| FPAY | Annual fee payment |
Payment date: 20170103 Year of fee payment: 5 |
|
| FPAY | Annual fee payment |
Payment date: 20190104 Year of fee payment: 7 |