CN115998945A - Preparation method and application of multifunctional hydrogel patch carrying drug controlled release microspheres - Google Patents
Preparation method and application of multifunctional hydrogel patch carrying drug controlled release microspheres Download PDFInfo
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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
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Abstract
The invention belongs to the field of medicine, and in particular relates to a preparation method and application of a multifunctional hydrogel patch carrying drug controlled release microspheres. Firstly, a preparation method of a multifunctional hydrogel patch carrying drug controlled release microspheres is disclosed, which sequentially comprises the following steps: setting up a single emulsion capillary microfluidic device, preparing MSNs for loading medicines, preparing an internal phase solution and an external phase solution, generating an aqueous phase solution with oil phase liquid drops dispersed therein, and preparing a multifunctional hydrogel patch for loading medicine controlled release microspheres. The invention provides a preparation method of a multifunctional hydrogel patch carrying drug controlled release microspheres, which can endow the patch with different biological functions by loading different drug active molecules in the microspheres and/or doping different functional nano materials in a hydrogel matrix, so that the patch has great application value in all aspects of accelerating the healing process aiming at each link of occurrence and development of chronic wounds.
Description
Technical Field
The invention belongs to the field of medicine, and in particular relates to a preparation method and application of a multifunctional hydrogel patch carrying drug controlled release microspheres.
Background
Wound healing is a complex, highly coordinated process that is critical to maintaining the barrier function of the skin. However, the various links involved in the normal healing process are disturbed by intrinsic disease states (diabetes, advanced age and immune disorders) or extrinsic factors (vascular insufficiency, microbial infection and sustained pressure effects), leading to the formation of chronic wounds. Such chronic wounds can lead to delayed healing or non-healing, causing serious discomfort and pain to the patient, while consuming significant medical and social resources.
Hydrogels are three-dimensional crosslinked networks of hydrophilic polymers that are capable of storing large amounts of moisture without dissolution. Hydrogels have become one of the most promising materials in wound management because of their structure similar to the extracellular matrix of the human body, the ability to absorb large amounts of exudates while maintaining wound wetting, providing a matrix for controlling drug delivery, and positive intervention in the healing process. However, many wound repair materials based on hydrogel have single functions, and cannot be used for a plurality of links of occurrence and development of chronic wounds, so that the clinical treatment effect is poor.
Disclosure of Invention
Although the clear mechanism of chronic wounds is still not fully revealed, excessive inflammatory reactions, oxidative stress, limited local blood flow and bacterial infections are considered to be major causes. Therefore, aiming at the morbidity links, the invention provides a preparation method and application of a multifunctional hydrogel patch carrying drug controlled release microspheres. The patch is prepared in one step by using a microfluidic technology and comprises a multi-stage structure and multiple components. The patch comprises a hydrogel matrix composed of alginate (alginate, alg) and methacryloylated gelatin (gelatin methacryloyl, gelMA), wherein one surface is loaded with drug controlled release microspheres composed of mesoporous silica nanoparticles (mesoporous silica nanoparticles, MSNs) and polylactic-co-glycolic acid copolymer (PLGA). By respectively loading different active drugs and nano materials in the drug controlled release microsphere and the hydrogel matrix, the patch can be endowed with unique biological functions of regulating immune inflammatory reaction, scavenging oxygen free radicals, promoting local neovascularization, resisting bacterial invasion and the like, so that the healing repair process is promoted in all aspects aiming at a plurality of links of the occurrence and development of chronic wounds.
The invention aims at overcoming the defects of the existing artificial repair materials and preparation technology, and provides a preparation method and application of a multifunctional hydrogel patch carrying drug controlled release microspheres. The invention is based on the powerful droplet control capability of the microfluidic technology, the excellent drug loading and controlled release capability of MSNs/PLGA microspheres, the excellent biocompatibility of Alg/GelMA hydrogel and the capability of promoting cell proliferation, and the multifunctional hydrogel patch carrying the drug controlled release microspheres is prepared, so that the repair process of chronic wounds can be accelerated.
Specifically, the technical scheme of the invention is as follows:
the invention discloses a preparation method of a multifunctional hydrogel patch carrying drug controlled release microspheres, which comprises the following steps:
s1, constructing a single emulsion capillary microfluidic device;
s2, preparing MSNs loaded with medicines;
s3, dispersing 0.5-2% of drug-loaded MSNs in 5-15% of PLGA dichloromethane solution by ultrasonic to obtain an internal phase solution;
s4, dispersing the nano material in a mixed aqueous solution of 0.2-1% of Alg and 10-20% of GelMA by ultrasonic waves, and adding a photoinitiator into the mixed aqueous solution to obtain an external phase solution;
s5, generating an aqueous phase solution in which oil phase liquid drops are dispersed: the inner phase solution and the outer phase solution are respectively injected into corresponding channels of the single emulsion capillary microfluidic device in the S1 to generate monodisperse oil-in-water droplets; collecting the generated droplets by a container prepared from polydimethylsiloxane to obtain an Alg/GelMA precursor solution in which MSNs/PLGA droplets are uniformly dispersed;
s6, preparing a multifunctional hydrogel patch carrying the drug controlled release microspheres: the aqueous phase solution generated in the step S5 is irradiated by ultraviolet light and soaked by calcium chloride, and is solidified to form Alg/GelMA hydrogel; ventilating and volatilizing dichloromethane at normal temperature to form MSNs/PLGA medicine controlled release microsphere; and then the multifunctional hydrogel patch carrying the drug controlled release microspheres is obtained by a freeze drying method.
In some preferred embodiments of the present invention, a method for preparing a multifunctional hydrogel patch carrying drug controlled release microspheres comprises the steps of:
s1, constructing a single emulsion capillary microfluidic device;
s2. Preparation of drug loaded MSNs: immersing 5% MSNs in a solution containing a certain amount of medicine, and centrifuging and drying after 24 hours;
s3, preparing an internal phase solution: 1% drug loaded MSNs are ultrasonically dispersed in 10% PLGA in methylene chloride;
s4, preparing an external phase solution: ultrasonically dispersing a certain amount of nano material in a mixed aqueous solution of 0.5% Alg and 15% GelMA, and adding a photoinitiator into the mixed aqueous solution;
s5, generating an aqueous phase solution in which oil phase liquid drops are dispersed: the inner phase solution and the outer phase solution are respectively injected into corresponding channels of the microfluidic device; adjusting the flow rates of the internal phase and the external phase solutions, and generating monodisperse oil-in-water droplets by using the fluid shear force between the two phases; the resulting droplets were collected using a vessel prepared from Polydimethylsiloxane (PDMS) to obtain an Alg/GelMA precursor solution (shown in fig. 1) with uniformly dispersed MSNs/PLGA droplets;
s6, preparing a multifunctional hydrogel patch carrying the drug controlled release microspheres: firstly, soaking an Alg/GelMA precursor solution of MSNs/PLGA liquid drops generated in S5 with ultraviolet light irradiation and calcium chloride, and curing to form Alg/GelMA hydrogel; then, the methylene dichloride is volatilized through ventilation at normal temperature, and oil phase liquid drops are further solidified, so that MSNs/PLGA drug controlled release microspheres are formed; finally, the multifunctional hydrogel patch carrying the drug controlled release microspheres is finally obtained by a freeze drying method (shown in figure 2).
Preferably, in S2, the drug is an angiogenesis promoting drug, an antibacterial drug, or a traditional Chinese medicine active ingredient that regulates immune inflammatory response.
Further, in S2, the drug may be an angiogenesis promoting drug such as Deferoxamine (DFO), dimethyloxalylglycine (DMOG), an antibacterial drug such as vancomycin and ciprofloxacin, or a traditional Chinese medicine active ingredient such as curcumin (Cur) and tea polyphenol for regulating immune inflammatory reaction.
Further, in S4, the hydrogel precursor solution may be doped with one or more functionalized nanomaterials, such as silver nanoparticles (silver nanoparticles, agNPs), polydopamine nanoparticles (polydopamine nanoparticles, PDANPs), or copper-containing metal-organic framework compounds (metal organic frameworks, MOFs).
Further, in S4, the GelMA may be replaced with at least one of methacryloylated hyaluronic acid (hyaluronic acid methacryloyl, HAMA), methacryloylated silk fibroin (silk fibroin methacryloyl, silMA).
Further, the photoinitiator of S4 is 2-hydroxy-2-methylpropionacetone (HMPP).
Further, in S5, the size of the MSNs/PLGA droplets can be controlled by adjusting the flow rates of the inner and outer phase solutions in the microfluidic device, with the diameter of the droplets increasing with increasing inner phase flow rate and decreasing with increasing outer phase flow rate. Therefore, the micro-fluidic technology can be used for accurately grasping the ratio of the drug controlled-release microspheres in the patch in the hydrogel matrix.
In step S6, the multifunctional hydrogel patch carrying the drug controlled release microsphere is in a shape of a cake. More preferably, the bottom diameter is 1.5. 1.5 cm and the height is 0.5. 0.5 cm.
Further, in S6, the diameter of the drug controlled release microsphere in the patch is in the range of 170-230 μm.
Further, in S1, the method for constructing the single-emulsion microfluidic generating device includes:
(1) Inner phase tube, outer phase tube and observation tube were prepared:
using a microelectrode controller to thin a glass capillary with an outer diameter of 1000 mu m and an inner diameter of 580 mu m, and then manually polishing the glass capillary into a pointed capillary with an inner diameter of 150 mu m by using sand paper to serve as an internal phase tube of the microfluidic single emulsion generating device; in addition, a glass capillary tube with the outer diameter of 1000 mu m and the inner diameter of 580 mu m is taken, and two ends of the capillary tube are polished smoothly by sand paper to be used as an outer phase tube of the microfluidic single emulsion generating device; the third glass capillary is a square tube with the inner diameter of 1200 mu m, and the square tube is used as an observation tube for generating liquid drops after being polished smoothly by sand paper; soaking the inner phase tube, the outer phase tube and the observation tube in ethanol solution, ultrasonically cleaning for 5-10 min, taking out, and blow-drying with nitrogen or air-drying at normal temperature;
(2) Building a microfluidic single emulsion generating device:
cutting a glass slide to a matched size according to the lengths of the inner phase tube and the outer phase tube, fixing a square tube in the middle area of the glass slide by using quick-drying adhesive, embedding the inner phase tube and the outer phase tube obtained in the step (1) into the observation tube obtained in the step (1) after the gel is fixed, inserting the tip of the inner phase tube into the outer phase tube, aligning the middle lines of the inner phase tube and the outer phase tube, fixing by using quick-drying adhesive, and finally carving a groove at the bottom of a flat-head needle head to enable the flat-head needle head to be stably erected above the joint of the inner phase tube, the outer phase tube and the observation tube, and fixing and sealing by using quick-drying adhesive to obtain the single-emulsion microfluidic generating device.
The invention discloses a multifunctional hydrogel patch carrying drug controlled release microspheres, which is prepared by the method.
The invention provides a multifunctional hydrogel patch carrying drug controlled release microspheres, which is prepared by the method and comprises a microsphere part and a hydrogel matrix part of the patch. The patch prepared by loading different pharmaceutically active molecules in the microspheres and/or doping different functional nano materials in the hydrogel matrix has the functions of resisting oxidative stress, regulating inflammatory reaction, promoting neovascularization, preventing microbial invasion and the like, so that the healing process is accelerated in all aspects aiming at each link of the occurrence and development of chronic wounds.
The third aspect of the invention discloses application of the multifunctional hydrogel patch carrying the drug controlled release microsphere in the medical field. Preferably, the invention also provides application of the multifunctional hydrogel patch carrying the drug controlled release microsphere in the field of chronic wound repair.
Compared with the prior art, the invention has the following beneficial effects:
(1) The invention provides a preparation method of a multifunctional hydrogel patch carrying drug controlled release microspheres, which is characterized in that a single emulsion template is generated by a microfluidic technology, ultraviolet light is combined, ion exchange and solvent volatilization are combined, and the multifunctional hydrogel patch carrying drug controlled release microspheres is prepared in one step, so that the preparation method is simple to operate, controllable in structure, low in cost and capable of realizing stable mass production.
(2) The multifunctional hydrogel patch carrying the drug controlled release microspheres prepared based on the microfluidic technology can adjust the size of a droplet template by adjusting the flow rate of an inner phase solution and an outer phase solution in a microfluidic device, so that the ratio of the drug controlled release microspheres to the hydrogel matrix in the patch is accurately controlled, and the problems of single structure, uncontrollable property, poor monodispersity and the like of the traditional hydrogel patch are solved.
(3) The invention uses MSNs and PLGA as main components of the drug controlled release microsphere in the patch. The medicine loading rate of the microsphere can be obviously improved by utilizing the mesoporous structure of MSNs (mesoporous silica nano particles), and the effect of the property of the medicine is avoided; with a degradable matrix of PLGA, it is possible to further encapsulate drugs effectively and control their release rate.
(4) The present invention uses Alg and GelMA as the main components of the hydrogel matrix in the patch. Alg has good biocompatibility, and GelMA can provide a cell adhesion site, so that the adhesion, migration and proliferation of epithelial cells at an implantation site are effectively promoted, and the healing process is quickened.
(5) The multifunctional hydrogel patch carrying the drug controlled release microspheres can endow the patch with different biological functions by loading different drug active molecules in the microspheres and/or doping different functional nanomaterials in a hydrogel matrix, for example: resist oxidative stress, regulate inflammatory reaction, promote neovascularization, prevent microbial invasion, etc., thereby accelerating the healing process in all aspects aiming at each link of the occurrence and development of chronic wounds, and having great application value.
Drawings
FIG. 1 is a schematic illustration of a process for preparing a multi-functional hydrogel patch of the present invention carrying controlled release microspheres of a drug;
FIG. 2 is a physical view of a multifunctional hydrogel patch carrying controlled release microspheres of a drug according to the present invention;
FIG. 3 is a schematic illustration of the inhibition of E.coli by a multifunctional hydrogel patch carrying controlled release drug microspheres;
FIG. 4 is a schematic illustration of the effect of a multifunctional hydrogel patch carrying controlled release drug microspheres to promote vascular endothelial cell formation into a tubular structure;
fig. 5 is a schematic diagram showing the effect of the multifunctional hydrogel patch carrying the drug controlled release microspheres on promoting the healing of chronic wound surfaces of diabetic mice.
Detailed Description
The technical solution of the present invention will be described in detail below with reference to the drawings and examples, but the present invention is not limited to the scope of the examples.
The experimental methods, in which specific conditions are not noted in the following examples, were selected according to conventional methods and conditions, or according to the commercial specifications. The reagents and materials used in the present invention are commercially available.
Example 1
A multifunctional hydrogel patch carrying drug controlled release microspheres is provided, wherein MSNs/PLGA drug controlled release microspheres in the patch are used for carrying angiogenesis promoting drugs DFO, and AgNPs with antibacterial effect are doped in Alg/GelMA hydrogel matrix. Thus, the patch prepared in this example has the dual function of promoting chronic wound neovascularization and preventing microbial invasion. The preparation method comprises the following steps:
s1, constructing a single emulsion capillary microfluidic device;
s2, preparing MSNs loaded with DFO: immersing 5% MSNs in an aqueous solution containing 10 mg/mL DFO, centrifuging and drying after 24 hours to obtain DFO-MSNs;
s3, preparing an internal phase solution: 1% DFO-MSNs were sonicated in 10% PLGA in dichloromethane;
s4, preparing an external phase solution: 100 ppm AgNPs were ultrasonically dispersed in a mixed aqueous solution of 0.5% Alg and 15% GelMA, and 1% HMPP was added thereto;
s5, generating an aqueous phase solution in which oil phase liquid drops are dispersed: the inner phase solution and the outer phase solution are respectively injected into corresponding channels of the microfluidic device; adjusting the flow rates of the internal phase and the external phase solutions, and generating monodisperse oil-in-water droplets by using the fluid shear force between the two phases; collecting the generated droplets by a container prepared from PDMS to obtain AgNPs/Alg/GelMA precursor solution in which the DFO-MSNs/PLGA droplets are uniformly dispersed;
s6, preparing a multifunctional hydrogel patch carrying the drug controlled release microspheres: firstly, the AgNPs/Alg/GelMA precursor solution generated in the step S5 is irradiated by ultraviolet light and soaked in calcium chloride, and is solidified to form AgNPs/Alg/GelMA hydrogel; then, the methylene dichloride is volatilized through ventilation at normal temperature, and oil phase liquid drops are further solidified, so that the DFO-MSNs/PLGA drug controlled release microspheres are formed; finally, the multifunctional hydrogel patch carrying the drug controlled release microspheres is finally obtained by a freeze drying method.
Example 2
A multifunctional hydrogel patch carrying drug controlled release microspheres is provided, wherein MSNs/PLGA drug controlled release microspheres in the patch are used for loading a traditional Chinese medicine active ingredient Cur capable of regulating immune inflammatory reaction, and PDANPs with an antioxidant effect are doped in an Alg/GelMA hydrogel matrix. Thus, the patch prepared in this example has the dual functions of modulating the local immunoinflammatory response level of chronic wounds and scavenging excess oxygen free radicals. The preparation method comprises the following steps:
s1, constructing a single emulsion capillary microfluidic device;
s2, preparing MSNs loaded with Cur: immersing 5% MSNs in an ethanol solution containing 10 mg/mL Cur, centrifuging and drying after 24 hours to obtain Cur-MSNs;
s3, preparing an internal phase solution: 1% Cur-MSNs are ultrasonically dispersed in 10% PLGA in methylene dichloride solution;
s4, preparing an external phase solution: 1% PDANPs were ultrasonically dispersed in a mixed aqueous solution of 0.5% Alg and 15% GelMA, and 1% HMPP was added thereto;
s5, generating an aqueous phase solution in which oil phase liquid drops are dispersed: the inner phase solution and the outer phase solution are respectively injected into corresponding channels of the microfluidic device; adjusting the flow rates of the internal phase and the external phase solutions, and generating monodisperse oil-in-water droplets by using the fluid shear force between the two phases; collecting the generated droplets by a container prepared from PDMS to obtain PDANPs/Alg/GelMA precursor solution in which Cur-MSNs/PLGA droplets are uniformly dispersed;
s6, preparing a multifunctional hydrogel patch carrying the drug controlled release microspheres: firstly, the aqueous phase solution generated in the step S4 is irradiated by ultraviolet light and soaked by calcium chloride, and is solidified to form PDANPs/Alg/GelMA hydrogel; then, the methylene dichloride is volatilized through ventilation at normal temperature, and oil phase liquid drops are further solidified, so that Cur-MSNs/PLGA drug controlled release microspheres are formed; finally, the multifunctional hydrogel patch carrying the drug controlled release microspheres is finally obtained by a freeze drying method.
Test example 1: antibacterial effect of multifunctional hydrogel patch carrying drug controlled release microspheres
Taking the multifunctional hydrogel patch carrying the drug controlled release microspheres prepared in example 1 as an example, the antibacterial ability of the patch was evaluated by applying a method of live/dead bacterial staining. In the experiment, a common chronic wound infection bacterium (escherichia coli, ATCC 25922) is selected as a test strain, and a hydrogel patch which is not doped with AgNPs is selected as a control group. The specific experimental method is as follows: placing the sample into 30 mL liquid culture medium containing escherichia coli suspension, and placing the liquid culture medium into a constant-temperature shaking table at 37 ℃ for 24 hours; centrifuging and washing 5 mL bacterial suspensions from a control group and an experimental group respectively, and then staining by using a live/dead bacterial staining kit; and (3) incubating for 15 minutes in a dark place, then taking 20 mu L of dyed bacterial suspension, dripping the bacterial suspension on a glass slide, and observing by using a fluorescence microscope. As shown in fig. 3, the living bacteria are stained green, the dead bacteria are stained red, the number of bacterial deaths of the experimental group is obviously greater than that of the control group, and the multifunctional hydrogel patch carrying the drug controlled release microspheres prepared in example 1 has remarkable antibacterial capability.
Test example 2: multifunctional hydrogel patch carrying drug controlled release microspheres for promoting angiogenesis
Taking the multifunctional hydrogel patch carrying the drug controlled release microspheres prepared in example 1 as an example, the angiogenesis promoting capacity of the patch was evaluated by using a vascular endothelial cell (human umbilical vein endothelial cells, HUVECs) tube test of human umbilical veins. The specific experimental method is as follows: 100. the micro L matrigel is flatly paved at the bottom of a 48-pore plate, and incubated for 1 hour in a constant temperature incubator at 37 ℃; 3X 10 of the additive was added per well 4 HUVECs, subsequently divided into experimental and control groups; HUVECs in the experimental group are co-cultured with the multifunctional hydrogel patch carrying the drug controlled release microsphere prepared in the example 1, and HUVECs in the control group are co-cultured with the hydrogel patch not carrying the DFO;after 12 hours the microscope observed that the two groups of cells formed a tubular structure. As shown in fig. 4, the experimental group HUVECs formed a significantly more tubular structure than the control group, demonstrating the ability of the multifunctional hydrogel patch carrying the drug controlled release microspheres prepared in example 1 to promote angiogenesis.
Test example 3: multifunctional hydrogel patch carrying drug controlled release microspheres and function of accelerating chronic wound healing
Taking the multifunctional hydrogel patch carrying the drug controlled release microspheres prepared in the example 1 as an example, the effect of the patch on accelerating chronic wound healing is evaluated by applying a diabetic mouse back wound model. The specific experimental method is as follows: the intraperitoneal injection of streptozotocin induces the C57BL/6J mice to form type I diabetes; a puncher with the diameter of 10 mm is used for manufacturing a round chronic wound surface with full-thickness skin defect on the back of each diabetic mouse; the method comprises the steps of dividing the method into an experimental group and a control group, wherein the experimental group covers a wound surface by using the multifunctional hydrogel patch carrying the drug controlled release microspheres prepared in the embodiment 1, and the control group covers the wound surface by using common medical gauze; wound healing was observed and recorded on days 0, 4, 7, 10, 14 post-operatively for each group of mice. As shown in fig. 5, at each observation time point, the healing area of the chronic wound of the experimental group is obviously larger than that of the control group, and the multifunctional hydrogel patch carrying the drug controlled release microspheres prepared in example 1 has the effect of promoting the healing of the chronic wound.
Therefore, the multifunctional hydrogel patch carrying the drug controlled release microspheres for chronic wound repair is prepared by one-step microfluidic technology, and the main components of the multifunctional hydrogel patch are hydrogel matrixes composed of Alg and GelMA, wherein the drug controlled release microspheres composed of MSNs and PLGA are carried on one surface of the hydrogel matrixes. The patch has simple and stable preparation process and high repeatability, and meets the industrial production requirement and clinical application standard. By loading different active molecules in the drug-loaded microspheres and/or doping different functional nano materials in the hydrogel matrix, the patch can have unique biological functions of regulating immune inflammatory reaction, scavenging oxygen free radicals, promoting local neovascularization, resisting bacteria invasion and the like, so that healing and repairing processes are promoted in all aspects aiming at a plurality of links of occurrence and development of chronic wounds.
The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.
Claims (10)
1. The preparation method of the multifunctional hydrogel patch carrying the drug controlled release microspheres comprises the following steps:
s1, constructing a single emulsion capillary microfluidic device;
s2, preparing MSNs loaded with medicines;
s3, dispersing 0.5-2% of drug-loaded MSNs in 5-15% of PLGA dichloromethane solution by ultrasonic to obtain an internal phase solution;
s4, dispersing the nano material in a mixed aqueous solution of 0.2-1% of Alg and 10-20% of GelMA by ultrasonic waves, and adding a photoinitiator into the mixed aqueous solution to obtain an external phase solution;
s5, generating an aqueous phase solution in which oil phase liquid drops are dispersed: the inner phase solution and the outer phase solution are respectively injected into corresponding channels of the single emulsion capillary microfluidic device in the S1 to generate monodisperse oil-in-water droplets; collecting the generated droplets by a container prepared from polydimethylsiloxane to obtain an Alg/GelMA precursor solution in which MSNs/PLGA droplets are uniformly dispersed, namely an aqueous phase solution in which oil phase droplets are dispersed;
s6, preparing a multifunctional hydrogel patch carrying the drug controlled release microspheres: the aqueous phase solution generated in the step S5 is irradiated by ultraviolet light and soaked by calcium chloride, and is solidified to form Alg/GelMA hydrogel; ventilating and volatilizing dichloromethane at normal temperature to form MSNs/PLGA medicine controlled release microsphere; and then the multifunctional hydrogel patch carrying the drug controlled release microspheres is obtained by a freeze drying method.
2. The method according to claim 1, wherein in S2 the drug is a pro-angiogenic drug, an antibacterial drug or a traditional Chinese medicine active ingredient regulating immune inflammatory response.
3. The method of claim 2, wherein the pro-angiogenic drug comprises deferoxamine, dimethyloxaloglycine; and/or
The antibacterial drug comprises vancomycin or ciprofloxacin; and/or
The traditional Chinese medicine active ingredients for regulating immune inflammatory reaction comprise curcumin or tea polyphenol.
4. The method according to claim 1, wherein in S4 the nanomaterial comprises silver nanoparticles, polydopamine nanoparticles or a copper-containing metal organic framework compound.
5. The method according to claim 1, wherein in S4 the GelMA is replaced with at least one of methacryloylated hyaluronic acid, methacryloylated silk protein.
6. The method of claim 1, wherein in S4, the photoinitiator is 2-hydroxy-2-methylpropionacetone.
7. The method of claim 1, wherein in S6, the drug-controlled-release microsphere-loaded multi-functional hydrogel patch is in the shape of a pie.
8. The method according to claim 1, wherein in S6, the diameter of the drug controlled release microspheres in the drug controlled release microsphere-loaded multifunctional hydrogel patch is in the range of 170-230 μm.
9. A multifunctional hydrogel patch carrying controlled release microspheres of a drug prepared according to any one of claims 1-8.
10. Use of the drug-loaded controlled-release microsphere multifunctional hydrogel patch according to claim 9 in the medical field.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117159801A (en) * | 2023-09-12 | 2023-12-05 | 中国人民解放军总医院第七医学中心 | Preparation method of nanometer composite hydrogel scaffold for promoting bone tissue regeneration by slowly releasing OPG and SDF-1 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107185029A (en) * | 2017-05-24 | 2017-09-22 | 南京大学 | A kind of macromolecule hydrogel embolism microball for wrapping up medicament-carried nano material and its preparation method and application |
| CN112354008A (en) * | 2020-11-02 | 2021-02-12 | 中国科学院大学温州研究院(温州生物材料与工程研究所) | Biological patch with anisotropic wettability and preparation method thereof |
| CN113372465A (en) * | 2021-06-25 | 2021-09-10 | 苏州浩微生物医疗科技有限公司 | Modified sodium hyaluronate, preparation method and microspheres prepared by using modified sodium hyaluronate |
| CN113429554A (en) * | 2021-06-25 | 2021-09-24 | 苏州浩微生物医疗科技有限公司 | Polymer microsphere, preparation method and drug-loading application thereof |
| US20220168472A1 (en) * | 2019-03-13 | 2022-06-02 | Susmita Bose | Enzyme-degradable hydrogel for delivery of a payload |
-
2023
- 2023-01-04 CN CN202310008161.4A patent/CN115998945A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107185029A (en) * | 2017-05-24 | 2017-09-22 | 南京大学 | A kind of macromolecule hydrogel embolism microball for wrapping up medicament-carried nano material and its preparation method and application |
| US20220168472A1 (en) * | 2019-03-13 | 2022-06-02 | Susmita Bose | Enzyme-degradable hydrogel for delivery of a payload |
| CN112354008A (en) * | 2020-11-02 | 2021-02-12 | 中国科学院大学温州研究院(温州生物材料与工程研究所) | Biological patch with anisotropic wettability and preparation method thereof |
| CN113372465A (en) * | 2021-06-25 | 2021-09-10 | 苏州浩微生物医疗科技有限公司 | Modified sodium hyaluronate, preparation method and microspheres prepared by using modified sodium hyaluronate |
| CN113429554A (en) * | 2021-06-25 | 2021-09-24 | 苏州浩微生物医疗科技有限公司 | Polymer microsphere, preparation method and drug-loading application thereof |
Non-Patent Citations (2)
| Title |
|---|
| GASEK, N, 等: "Development of alginate and gelatin-based pleural and tracheal sealants", ACTA BIOMATERIALIA, vol. 131, 1 September 2021 (2021-09-01), pages 222 - 235, XP086746874, DOI: 10.1016/j.actbio.2021.06.048 * |
| JUNG, H, 等: "Adhesive Hydrogel Patch with Enhanced Strength and Adhesiveness to Skin for Transdermal Drug Delivery", ADVANCED FUNCTIONAL MATERIALS, vol. 30, no. 42, 15 October 2020 (2020-10-15), XP072410119, DOI: 10.1002/adfm.202070280 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117159801A (en) * | 2023-09-12 | 2023-12-05 | 中国人民解放军总医院第七医学中心 | Preparation method of nanometer composite hydrogel scaffold for promoting bone tissue regeneration by slowly releasing OPG and SDF-1 |
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