CN110917489A - Antibacterial chitosan microneedle and application thereof - Google Patents
Antibacterial chitosan microneedle and application thereof Download PDFInfo
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- CN110917489A CN110917489A CN201911381855.2A CN201911381855A CN110917489A CN 110917489 A CN110917489 A CN 110917489A CN 201911381855 A CN201911381855 A CN 201911381855A CN 110917489 A CN110917489 A CN 110917489A
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- microneedle
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
-
- 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
- A61M2037/0046—Solid 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
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention discloses an antibacterial chitosan microneedle and application thereof. The preparation method of the antibacterial chitosan microneedle comprises the following steps: s1, dissolving chitosan in water, and removing bubbles in vacuum to obtain a chitosan solution; s2, coating the chitosan solution obtained in the step S1 on a PDMS microneedle mould, filling, drying and stripping to obtain the antibacterial chitosan microneedle. The microneedle has the effect of remarkably inhibiting the growth of escherichia coli and staphylococcus aureus, can effectively prevent bacteria from entering a body through a micro-channel on the skin to cause bacterial infection, and solves the problem that the microneedle is easy to cause bacterial infection on the skin in the using process; in addition, the microneedle has the advantages of simple preparation method and low cost, can be biodegraded after penetrating into the skin, can not leave microneedle residues in vivo, and has wide application prospect when being used as a transdermal drug delivery carrier.
Description
Technical Field
The invention belongs to the technical field of micro-nano manufacturing. More particularly, relates to an antibacterial chitosan microneedle and an application thereof.
Background
The micro-needle can puncture the stratum corneum of human skin (puncture the upper part of the epithelial layer and the dermis layer) to deliver the medicament into the body, does not stimulate nerves in the skin, and has the characteristics of no pain, minimal invasion and the like. Various types of microneedles have been developed, including soluble microneedles, solid microneedles, coated microneedles, hollow microneedles, and hydrogel microneedles; the soluble microneedle consists of water-soluble polymers, can be completely dissolved in body fluid after piercing the skin, and can not leave microneedle residues in the body; in addition, the soluble microneedle also has the advantages of good biocompatibility, large drug-loading rate and the like. Therefore, the soluble microneedles are widely used in transdermal drug delivery.
However, transdermal drug delivery via microneedles may lead to bacterial infections; studies have shown that bacteria adhere to microneedles more readily than hypodermic needles, and that the adherence of bacteria to microneedles is an order of magnitude greater than that of hypodermic needles. In addition, microneedles can form microchannels in the stratum corneum during drug delivery, thereby disrupting the integrity of the skin, and bacteria can also enter the skin through these microchannels, resulting in limited use of microneedles in the medical field.
Therefore, the prepared microneedle has high safety and an antibacterial function, prevents bacteria from entering a body through the microchannel on the skin to cause bacterial infection, improves the safety of the microneedle in use, and has important significance for wide popularization and use of the microneedle in the medical field.
Disclosure of Invention
The invention aims to solve the technical problem of overcoming the defect and the defect that the existing micro-needle is easy to cause skin infection with bacteria in the using process, and provides an antibacterial chitosan micro-needle and application thereof.
The invention aims to provide an antibacterial chitosan microneedle.
The invention also aims to provide the application of the microneedle serving as a transdermal drug delivery carrier.
The above purpose of the invention is realized by the following technical scheme:
the invention firstly provides an antibacterial chitosan microneedle, and the preparation method comprises the following steps:
s1, dissolving chitosan in water, and removing bubbles in vacuum to obtain a chitosan solution;
s2, coating the chitosan solution obtained in the step S1 on a PDMS microneedle mould, filling, drying and stripping to obtain the antibacterial chitosan microneedle.
Preferably, the chitosan of step S1 has a molecular weight of < 80 KDa.
When the molecular weight of chitosan is too high (> 80kDa), the solubility of chitosan is poor.
More preferably, the chitosan of step S1 has a molecular weight of 50 KDa.
Preferably, the mass-to-volume ratio of the chitosan to the water in the step S1 is 1-5: 50.
when the mass-volume ratio of chitosan to water is too low (< 1: 50), the whole piece of antibacterial chitosan microneedle with a uniform structure cannot be prepared by reverse molding; when the mass-to-volume ratio of chitosan to water is too high (> 1: 5), the prepared chitosan solution has poor flow property, which can hinder the normal operation of the microneedle inverse mould preparation process.
More preferably, the mass-to-volume ratio of chitosan to water in step S1 is 1: 25.
preferably, the amount of the coating in the step S2 is 0.1-0.4 mL/cm2。
More preferably, the amount of the spread in step S2 is 0.2mL/cm2。
Preferably, the filling of step S2 is vacuum filling.
Preferably, the vacuum filling conditions in step S2 are: vacuumizing to 0.04-0.08 MPa, maintaining the pressure for 2-3 min, deflating, and repeating for 3-4 times.
More preferably, the vacuum filling conditions in step S2 are: vacuumizing to 0.06MPa, maintaining the pressure for 2min, deflating, and repeating for 3 times.
Preferably, the microneedle comprises a microneedle body and a microneedle substrate, and the microneedle body comprises a microneedle body top and a microneedle body bottom.
More preferably, the length of the microneedle body is 150-500 μm, the diameter of the top of the microneedle body is 100-300 μm, and the diameter of the bottom of the microneedle body is 10-50 μm.
Still further preferably, the length of the microneedle body is 340 μm, the diameter of the top of the microneedle body is 250 μm, and the diameter of the bottom of the microneedle body is 25 μm.
Creative exploration experiments show that the microneedle prepared by the invention has the effect of obviously inhibiting the growth of escherichia coli and staphylococcus aureus; therefore, the application of the microneedle as a transdermal drug delivery carrier is also within the protection scope of the present invention.
The invention has the following beneficial effects:
the invention provides an antibacterial chitosan microneedle and application thereof. The antibacterial chitosan microneedle has a remarkable inhibiting effect on growth of escherichia coli and staphylococcus aureus, can effectively prevent bacteria from entering a human body through a microchannel on the skin to cause bacterial infection, solves the problem that the microneedle is easy to cause skin infection of the bacteria in the using process, uses a chitosan solution without toxicity, has rich raw material sources, and improves the using safety of the microneedle; in addition, the microneedle has the advantages of simple preparation method and low cost, can be biodegraded after penetrating into the skin, can not leave microneedle residues in vivo, and has wide application prospect when being used as a transdermal drug delivery carrier.
Drawings
Fig. 1 is a schematic view of an antibacterial chitosan microneedle according to the present invention; wherein, 1 represents a microneedle body, 10 represents a microneedle body top, and 11 represents a microneedle body bottom; and 2 represents a microneedle substrate.
Fig. 2 is the result of measuring the antibacterial performance of the microneedle of the present invention.
Detailed Description
The present invention is further illustrated by the following specific examples, which are not intended to limit the invention in any way. Reagents, methods and apparatus used in the present invention are conventional in the art unless otherwise indicated.
Unless otherwise indicated, reagents and materials used in the following examples are commercially available.
Example 1 antimicrobial chitosan microneedles
An antibacterial chitosan microneedle, the preparation method comprises the following steps:
s1, dissolving chitosan with the molecular weight of 50KDa in water (the mass-volume ratio of the chitosan to the water is 1: 25), and removing bubbles in vacuum to obtain a chitosan solution;
s2, the dosage of the chitosan solution obtained in the step S1 is 0.2mL/cm2Coating on a PDMS microneedle mould, vacuumizing to 0.06MPa, maintaining the pressure for 2min, deflating, repeating for 3 times, drying, and stripping to obtain the antibacterial chitosan microneedle; wherein the length of the microneedle is 340 μm, the diameter of the top of the microneedle body is 250 μm, and the diameter of the bottom of the microneedle body is 25 μm.
A schematic diagram of an antibacterial chitosan microneedle is shown in fig. 1.
Example 2 antimicrobial chitosan microneedles
An antibacterial chitosan microneedle, the preparation method comprises the following steps:
s1, dissolving chitosan with the molecular weight of 10KDa in water (the mass-volume ratio of the chitosan to the water is 1: 5), and removing bubbles in vacuum to obtain a chitosan solution;
s2, the dosage of the chitosan solution obtained in the step S1 is 0.1mL/cm2Coating on a PDMS microneedle mould, vacuumizing to 0.04MPa, maintaining the pressure for 3min, deflating, repeating for 4 times, drying, and stripping to obtain the antibacterial chitosan microneedle; wherein the length of the microneedle is 500 μm, the diameter of the top of the microneedle body is 300 μm, and the diameter of the bottom of the microneedle body is 50 μm.
Example 3 antimicrobial chitosan microneedles
An antibacterial chitosan microneedle, the preparation method comprises the following steps:
s1, dissolving chitosan with the molecular weight of 80KDa in water (the mass-volume ratio of the chitosan to the water is 1: 50), and removing bubbles in vacuum to obtain a chitosan solution;
s2, the dosage of the chitosan solution obtained in the step S1 is 0.4mL/cm2Coating on a PDMS microneedle mould, vacuumizing to 0.08MPa, maintaining the pressure for 2.5min, deflating, repeating for 3 times, drying, and stripping to obtain the antibacterial chitosan microneedle; wherein the length of the microneedle is 150 μm, the diameter of the top of the microneedle body is 100 μm, and the diameter of the bottom of the microneedle body is 10 μm.
Example 4 antimicrobial chitosan microneedles
An antibacterial chitosan microneedle, the preparation method comprises the following steps:
s1, dissolving chitosan with the molecular weight of 30KDa in water (the mass-volume ratio of the chitosan to the water is 1: 10), and removing bubbles in vacuum to obtain a chitosan solution;
s2, the dosage of the chitosan solution obtained in the step S1 is 0.3mL/cm2Spreading on a PDMS microneedle mould, vacuumizing to 0.07MPa, maintaining the pressure for 2min, deflating, repeating for 4 times, drying, and stripping to obtain the antibacterial chitosan microneedle; wherein the length of the microneedle is 340 μm, the diameter of the top of the microneedle body is 250 μm, and the diameter of the bottom of the microneedle body is 25 μm.
Example 5 antimicrobial chitosan microneedles
An antibacterial chitosan microneedle, the preparation method comprises the following steps:
s1, dissolving chitosan with the molecular weight of 70KDa in water (the mass-volume ratio of the chitosan to the water is 1: 35), and removing bubbles in vacuum to obtain a chitosan solution;
s2, the dosage of the chitosan solution obtained in the step S1 is 0.35mL/cm2Coating on a PDMS microneedle mould, vacuumizing to 0.05MPa, maintaining the pressure for 2.8min, deflating, repeating for 3 times, drying, and stripping to obtain the antibacterial chitosan microneedle; wherein the length of the microneedle is 250 μm, the diameter of the top of the microneedle body is 200 μm, and the diameter of the bottom of the microneedle body is 30 μm.
Taking example 1 as an example, the antibacterial performance of the antibacterial chitosan microneedle prepared by the invention is measured, and the specific experimental method and the experimental result are respectively as follows:
application example 1 measurement of antibacterial Properties of microneedles
1. Experimental methods
Firstly, sterilizing an LB agar culture medium in a sterilizing pot for 20min (121 ℃, 101kPa), cooling to 40-50 ℃, and pouring into a sterilized culture dish to prepare a flat plate; then, the sample (CS or CS-Zn (II) MNs, 1mg) was mixed with the bacterial suspension (10)6CFU mL-1Staphylococcus aureus and escherichia coli) were co-cultured in 48-well plates at 37 ℃ for 24 h; second, 100 μ L of diluted bacterial suspension (100-fold dilution) was spread on nutrient agar; finally, the culture dish is put inAfter incubation at 37 ℃ for 24h, colonies of Staphylococcus aureus and Escherichia coli were counted.
2. Results of the experiment
The results of the measurement of the antibacterial performance of the microneedles are shown in fig. 2, and it can be seen that, compared with the blank control, the microneedles have significant inhibitory effects on the growth of escherichia coli and staphylococcus aureus, and can effectively prevent bacteria from entering the body through microchannels on the skin to cause bacterial infection, and the raw material chitosan solution has high safety and wide application range.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (9)
1. An antibacterial chitosan microneedle is characterized in that the preparation method comprises the following steps:
s1, dissolving chitosan in water, and removing bubbles in vacuum to obtain a chitosan solution;
s2, coating the chitosan solution obtained in the step S1 on a PDMS microneedle mould, filling, drying and stripping to obtain the antibacterial chitosan microneedle.
2. A microneedle according to claim 1, wherein the chitosan of step S1 has a molecular weight < 80 KDa.
3. The microneedle according to claim 1, wherein the mass-to-volume ratio of the chitosan to the water in step S1 is 1 to 5: 50.
4. the microneedle according to claim 1, wherein the coating amount in step S2 is 0.1 to 0.4mL/cm2。
5. A microneedle according to claim 1, wherein said filling of step S2 is vacuum filling.
6. A microneedle according to claim 5, wherein the vacuum filling conditions of step S2 are: vacuumizing to 0.04-0.08 MPa, maintaining the pressure for 2-3 min, deflating, and repeating for 3-4 times.
7. A microneedle according to any one of claims 1 to 6, wherein the microneedle comprises a microneedle body and a microneedle base, and the microneedle body comprises a microneedle body top and a microneedle body bottom.
8. A microneedle according to claim 7, wherein the length of the microneedle body is 150 to 500 μm, the diameter of the top of the microneedle body is 100 to 300 μm, and the diameter of the bottom of the microneedle body is 10 to 50 μm.
9. Use of a microneedle according to any one of claims 1 to 8 as a transdermal delivery vehicle.
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Cited By (1)
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WO2022105824A1 (en) * | 2020-11-20 | 2022-05-27 | 南京鼓楼医院 | Preparation method and application for microneedle carrying live bacteria |
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CN104027324A (en) * | 2013-03-06 | 2014-09-10 | 中国科学院理化技术研究所 | Soluble microneedle vaccine patch and preparation method thereof |
WO2015186940A1 (en) * | 2014-06-02 | 2015-12-10 | 주식회사 아모그린텍 | Microneedle patch and production method therefor |
CN108969880A (en) * | 2018-06-12 | 2018-12-11 | 上海白衣缘生物工程有限公司 | A kind of solubility micropin film and preparation method thereof |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
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CN104027324A (en) * | 2013-03-06 | 2014-09-10 | 中国科学院理化技术研究所 | Soluble microneedle vaccine patch and preparation method thereof |
WO2015186940A1 (en) * | 2014-06-02 | 2015-12-10 | 주식회사 아모그린텍 | Microneedle patch and production method therefor |
CN108969880A (en) * | 2018-06-12 | 2018-12-11 | 上海白衣缘生物工程有限公司 | A kind of solubility micropin film and preparation method thereof |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2022105824A1 (en) * | 2020-11-20 | 2022-05-27 | 南京鼓楼医院 | Preparation method and application for microneedle carrying live bacteria |
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