CN111437437B - Polyacrylamide hydrogel dressing and preparation method and application thereof - Google Patents

Polyacrylamide hydrogel dressing and preparation method and application thereof Download PDF

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CN111437437B
CN111437437B CN202010487612.3A CN202010487612A CN111437437B CN 111437437 B CN111437437 B CN 111437437B CN 202010487612 A CN202010487612 A CN 202010487612A CN 111437437 B CN111437437 B CN 111437437B
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curcumin
polyacrylamide hydrogel
hydrogel dressing
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dressing
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CN111437437A (en
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董智贤
卢淑欣
陈雨歆
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    • AHUMAN NECESSITIES
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    • A61L26/0061Use of materials characterised by their function or physical properties
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
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    • A61L26/0066Medicaments; Biocides
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    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
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Abstract

The invention discloses a polyacrylamide hydrogel dressing which has good flexibility, elasticity and adhesiveness and can prevent wound surface bacterial infection; when in use, the curcumin can be slowly released to the external environment, and has the functions of long-acting anti-inflammation and sterilization; meanwhile, the change condition of the wound surface can be observed at any time through the dressing directly, and whether the wound surface is infected or not is monitored in time through color change; is a novel intelligent hydrogel wound dressing with antibacterial property and pH value responsiveness. According to the invention, a specific amount of polypropylene glycol is added as a curcumin carrier, and the polyacrylamide hydrogel dressing stably loaded with curcumin is directly prepared by adopting an oil-in-water emulsion template method, so that the preparation method is simple, the raw materials are wide in source, low in price and controllable in cost, and the preparation method can be applied to industrial production.

Description

Polyacrylamide hydrogel dressing and preparation method and application thereof
Technical Field
The invention relates to the technical field of hydrogel, in particular to a polyacrylamide hydrogel dressing and a preparation method and application thereof.
Background
The skin is the largest organ of the body and the most important barrier between the human body and the external environment, and any form of injury can lead to imbalance in homeostasis, which can lead to prolonged wound healing, severe disability, and even death if the rate of repair is slow, there is insufficient water, electrolyte imbalance, and infection. Appropriate wound dressings are needed to protect skin wounds from further damage, accelerate healing and control drug release. The hydrogel dressing is a good novel wound dressing, has good water absorption, can maintain the moist environment of a wound surface, has good moisture retention, air permeability and biocompatibility, and has wide application prospect in the field of antibacterial dressings.
At present, the domestic novel antibacterial hydrogel dressing mainly comprises: firstly, the hydrogel and the derivative hydrogel have antibacterial property, but the hydrogel prepared by only using chitosan has the problems of insufficient mechanical strength and the like, the hydrogel is required to be formed with other polymers in modes of interpenetrating and the like to enhance the mechanical strength and the crosslinking degree of the hydrogel, and when infection is serious, the antibacterial effect of the antibacterial hydrogel such as chitosan and the like has great limitation, and an antibacterial agent is required to be loaded to enhance the antibacterial effect; and secondly, the antibacterial agent-loaded hydrogel is a commonly used antibacterial agent loaded nano-silver with excellent performances such as good antibacterial property, heat resistance, good dispersibility, small drug resistance and the like, but the metal antibacterial agent has certain cytotoxicity and certain potential safety hazard in application.
The polyacrylamide hydrogel has good histocompatibility and biological inertia, is applied in the biomedical field for a long time, and is expected to be used for preparing wound dressings. Chinese patent application CN109513039A discloses an antibacterial hydrogel dressing containing imidazole bromide, which is prepared by uniformly dispersing antibacterial components of imidazole bromide, acrylamide and an initiator into a hydroxyl-containing hydrophilic polymer monomer solution to form a carrier system, and then heating and repeatedly freezing and thawing to enable the imidazole bromide to be tightly combined with matrix macromolecules through chemical bonds. Chinese patent applications CN109550073A and CN109481727A disclose that bismuth oxychloride or tungsten disulfide is dispersed in a sodium alginate solution, and then mixed with acrylamide, a cross-linking agent and an initiator to form a gel, so as to prepare an antibacterial hydrogel dressing, which has an antibacterial effect under a specific illumination condition. The patent discloses that organic synthetic drugs or inorganic metal compounds are selected as antibacterial agents, although the antibacterial effect is good, certain potential safety hazards exist; in addition, in order to ensure that the hydrogel has good load performance, mechanical properties and the like, a plurality of materials are required to be combined to form a composite hydrogel carrier, so that the preparation cost is high and the process is complex.
In order to realize a green and safe antibacterial hydrogel dressing, some natural antibacterial agents are good choices. Curcumin is a natural hydrophobic polyphenol compound extracted from the rhizome of some plants in the families of Zingiberaceae and Araceae. Due to the fact that two hydroxyl groups are arranged at two ends of a curcumin molecule, a conjugation effect of electron cloud deviation occurs under an alkaline condition, when the pH value is larger than 7.0, the curcumin is changed from yellow to rose red, and modern chemistry utilizes the property to serve as an acid-base indicator. Researches show that curcumin is a natural medicine with high safety (almost no toxicity to people and livestock), has good biological activity, and has the effects of wound repair, antibacterial property, oxidation resistance, inflammation diminishing and the like. But the curcumin has the characteristics of large molecular weight, difficult water solubility, poor stability, low bioavailability and the like, so that the curcumin has great difficulty in application to wound dressings.
Disclosure of Invention
The invention aims at providing a polyacrylamide hydrogel dressing which can stably load curcumin, can slowly release the curcumin for a long time when in use, has the functions of diminishing inflammation and sterilizing for a long time, and prevents wound surface bacterial infection; meanwhile, whether the wound surface is infected or not can be monitored directly and timely through color change.
The invention also aims to provide a preparation method of the polyacrylamide hydrogel dressing, which is simple and controllable in cost.
The invention is realized by the following technical scheme:
the polyacrylamide hydrogel dressing comprises the following components in parts by weight:
100 parts of acrylamide;
10-80 parts of polypropylene glycol;
0.02-1 part of a crosslinking agent;
0.1-1 part of redox initiator;
0.2-1 part of curcumin;
220-290 parts of water;
wherein the redox initiator comprises 0.05-0.70 parts of oxidant and 0.05-0.30 parts of reducing agent.
Preferably, the polyacrylamide hydrogel dressing comprises the following components in parts by weight:
100 parts of acrylamide;
20-60 parts of polypropylene glycol;
0.03-0.5 part of a crosslinking agent;
0.25-0.7 parts of redox initiator;
0.30-0.75 parts of curcumin;
250-270 parts of water;
wherein the redox initiator comprises 0.15-0.45 part of oxidant and 0.10-0.25 part of reducing agent.
The addition of a specific amount of polypropylene glycol enables the formation of a large number of micron-sized spherical pores in the polyacrylamide hydrogel. The number average molecular weight of the polypropylene glycol is 200-2000. The pore diameter of the holes formed by using the polypropylene glycol with a certain molecular weight is distributed in the range of 1-100 mu m, and the holes are intensively distributed in the range of 50-80 mu m, so that the curcumin can be stably loaded with a natural medicine curcumin with a larger molecular scale.
The porosity of the polyacrylamide hydrogel dressing is 20% -60%. The load capacity of curcumin of the polyacrylamide hydrogel dressing is 500-1000 mug/g.
The cross-linking agent is selected from any one of N, N' -methylene bisacrylamide or ethylene glycol dimethacrylate.
The oxidant is selected from any one of persulfate, chlorate or ammonium ceric nitrate; specifically, the persulfate can be ammonium persulfate and potassium persulfate; the chlorate salt may be sodium chlorate.
The reducing agent is selected from any one of N, N, N ', N' -tetramethylethylenediamine, sodium sulfite or thiourea;
the redox initiator is a combination of an oxidizing agent and a reducing agent. Preferably, the redox initiator is selected from any one of ammonium persulfate/N, N '-tetramethylethylenediamine, potassium persulfate/N, N' -tetramethylethylenediamine, ammonium persulfate/sodium sulfite, potassium persulfate/sodium sulfite, sodium chlorate/sodium sulfite, or ceric ammonium nitrate/thiourea.
The water is deionized water.
The invention also provides a preparation method of the polyacrylamide hydrogel dressing, which comprises the following steps:
(1) according to the proportion, acrylamide and a cross-linking agent are dissolved in water under the condition of ice bath at 0-5 ℃ by stirring to obtain a homogeneous phase aqueous solution;
(2) adding curcumin into polypropylene glycol according to a ratio, and performing ultrasonic dispersion at the temperature of 20-30 ℃ until the curcumin is fully dissolved, wherein the ultrasonic frequency is 25-80 KHz, so as to obtain a curcumin polypropylene glycol solution;
(3) adding the curcumin polypropylene glycol solution obtained in the step (2) into the homogeneous phase aqueous solution obtained in the step (1), and stirring for 0.5-2 hours at an ice bath temperature of 0-5 ℃ to form a uniformly dispersed emulsion; and introducing nitrogen flow into the emulsion for 30-60 s to remove oxygen, adding a redox initiator, continuously stirring for 10-30 min at the temperature of 0-5 ℃ in an ice bath to uniformly mix, and then sealing in the dark at the temperature of 20-30 ℃ to perform polymerization reaction for 4-24 h to obtain the curcumin-loaded polyacrylamide hydrogel dressing.
Magnetic stirring can be adopted for stirring, and the rotating speed of the magnetic stirring is 500-1000 r/min; the stirring magnetons need to be removed before the polymerization reaction.
The polymerization reaction in step (3) is carried out in a plastic mold. Other suitable molds may be used as the polymerization vessel to directly obtain the hydrogel dressing of the desired specific size and shape.
The method comprises the steps of firstly dissolving curcumin in polypropylene glycol to serve as an oil phase, adding the oil phase into a homogeneous phase aqueous solution mixed by an acrylamide monomer and a cross-linking agent, stirring to form a uniformly dispersed oil-in-water emulsion system, and then adding a redox initiator to carry out polymerization reaction to form hydrogel. By means of forming an oil-in-water emulsion system, the polypropylene glycol dissolved with the curcumin is uniformly dispersed in the hydrogel to form a large number of micron-sized spherical holes, so that the aim of stably loading the curcumin by polyacrylamide is fulfilled.
The polyacrylamide hydrogel dressing is yellow and transparent, is a novel intelligent hydrogel wound dressing with antibacterial property and PH value responsiveness, and can be applied to wounds such as trauma, burn, scald, ulcer and bedsore.
Compared with the prior art, the invention has the following beneficial effects:
(1) the selected polypropylene glycol has good biocompatibility, the curcumin can be stably dissolved in the polypropylene glycol, the stability of the curcumin is improved, and meanwhile, the polypropylene glycol can form a large number of micron-sized spherical holes in polyacrylamide hydrogel, so that the curcumin can be stably dispersed and loaded on the polyacrylamide hydrogel and can be slowly released when being used, and the problems that the curcumin has poor stability and water solubility and cannot be directly loaded on the polyacrylamide hydrogel are solved.
(2) The invention adopts an oil-in-water emulsion template method to prepare the polyacrylamide hydrogel dressing. The preparation method comprises the steps of firstly dissolving curcumin in polypropylene glycol as an oil phase, mixing acrylamide and a cross-linking agent, dissolving the mixture in deionized water as a water phase, mixing the oil phase and the water phase to form an oil-in-water emulsion system, finally adding a redox initiator, and carrying out polymerization reaction to obtain the polyacrylamide hydrogel dressing stably loaded with the curcumin.
(3) The polyacrylamide hydrogel dressing has good moisture retention and air permeability, is beneficial to maintaining the sterile environment of a wound surface and accelerating the regeneration of epithelium; the natural medicine curcumin is used as an antibacterial agent, has high safety, and has the effects of diminishing inflammation, sterilizing, infecting and promoting wound healing for a long time.
(4) The polyacrylamide hydrogel dressing has good mechanical property, good flexibility and elasticity, can form good adhesion with skin, and is suitable for wound surfaces of different parts of a body, in particular to frequently moving parts such as elbows, wrists, knees, ankles and the like.
(5) The polyacrylamide hydrogel dressing of the invention is yellow and transparent. Because the healthy skin or healed wound of the human body is weakly acidic, the pH value is about 5.0; when other complications occur, the skin environment becomes weak alkaline, and the pH value is increased to about 6.5-8.5; while curcumin changes from yellow to rose-red at pH > 7.0. When the polyacrylamide hydrogel dressing is used, the change condition of the wound can be observed directly through the dressing; and whether the wound is infected can be rapidly monitored according to the color change condition of curcumin in the dressing.
Drawings
FIG. 1 is a schematic diagram of the preparation of polyacrylamide hydrogel;
FIG. 2 is a photograph of a sample of gel 1 adhered to the skin surface;
FIG. 3 is a graph showing tensile properties of hydrogel samples of examples and comparative examples;
figure 4 is a graph of curcumin in vitro release test for gel 1 sample;
in fig. 5, A, B, C, D are optical micrographs at 50 x magnification of fresh sections of gel 1 before curcumin release, gel 1 after curcumin release for 120h, comparative sample 1 and comparative sample 2, respectively;
FIG. 6 is a fluorescent photomicrograph at 5X magnification of a sample before and after delayed release of gel 1 curcumin;
FIG. 7 is a graph showing the antibacterial effects of gel 1, control 1 and control 2 on Escherichia coli and Staphylococcus aureus; wherein, Panel A is E.coli cultured for 1 day (24 h); panel B is Staphylococcus aureus cultured for 1 day (24 h); FIG. C shows E.coli cultured for 5 days; panel D is Staphylococcus aureus cultured for 5 days; in the figure, 1, 2 and 3 correspond to gel 1, comparative sample 1 and comparative sample 2, respectively.
Detailed Description
The present invention will be described in detail with reference to specific examples. The following examples will assist those skilled in the art in further understanding the invention, but are not intended to limit the invention in any way. It should be noted that variations and modifications can be made by persons skilled in the art without departing from the spirit of the invention. All falling within the scope of the present invention.
The raw materials used in the invention are derived from commercial products:
(1) acrylamide: analytically pure, Tianjin, Tanshima chemical reagents, Inc.;
(2) polypropylene glycol 1: the number average molecular weight is 2000; a western reagent;
polypropylene glycol 2: the number average molecular weight is 1000; a western reagent;
(3) n, N' -methylenebisacrylamide: analytically pure, Shanghai Aladdin science and technology Co., Ltd;
(4) ammonium persulfate: analytically pure, Tianjin, Tanshima chemical reagents, Inc.;
(5) n, N' -tetramethylethylenediamine: analytical purification, Shanghai Michelin Biochemical technology, Inc.;
(6) curcumin: analytically pure, Shanghai Aladdin science and technology Co., Ltd;
(7) PBS phosphate buffer standard solution (pH = 7.2-7.4): sterile, Shanghai Aladdin science and technology, Inc.;
(8) nutrient agar medium plate: ready-to-use 90mmX20, Kyoto Loop Microscience, Inc.;
(9) staphylococcus aureus [ ATCC25923 ]: shanghai Lu micro-technology, Inc.;
(10) escherichia coli strain [ ATCC25922 ]: shanghai Lu micro-Tech Co., Ltd.
Determination of pore size and porosity:
the method for measuring the pore diameter and the porosity of the polyacrylamide macroporous hydrogel comprises the following steps: and observing and photographing a fresh section of the sample under an optical microscope, analyzing the aperture size and the hole area on the section picture of the gel, and analyzing three pictures of each sample. Porosity is the percentage of the total area of the pore area, and the average porosity is taken.
Example 1
(1) Dissolving 100 parts by weight of acrylamide and 0.06 part by weight of cross-linking agent N, N' -methylene bisacrylamide in 264 parts by weight of deionized water under the condition of ice bath at 3 ℃ by magnetic stirring to obtain homogeneous phase aqueous solution;
(2) adding 0.44 part of curcumin into 36 parts of polypropylene glycol 1 by weight, and performing ultrasonic dispersion at 25 ℃ until the curcumin is fully dissolved, wherein the ultrasonic frequency is 40KHz, so as to obtain a curcumin polypropylene glycol solution;
(3) adding the curcumin polypropylene glycol solution obtained in the step (2) into the homogeneous phase aqueous solution obtained in the step (1), and magnetically stirring for 2 hours at the temperature of 3 ℃ in an ice bath to form a uniformly dispersed emulsion; and introducing nitrogen flow into the emulsion for 30s to remove oxygen, then adding 0.18 part of ammonium persulfate and 0.12 part of N, N, N ', N' -tetramethyl ethylene diamine in sequence, keeping the stirring for 20min under the ice bath condition of 3 ℃ to uniformly mix, removing the ice bath and stirring magnetons, then pouring into a plastic mould, and carrying out dark sealing reaction for 24h at 25 ℃ to obtain the curcumin-loaded polyacrylamide hydrogel dressing. The appearance was yellow and transparent, and was designated as gel 1. The pore diameter is distributed in the range of 1 to 100 μm, and the porosity is about 50%.
Example 2
(1) Dissolving 100 parts by weight of acrylamide and 0.24 part by weight of cross-linking agent N, N' -methylene bisacrylamide in 278 parts by weight of deionized water at 3 ℃ under magnetic stirring to obtain a homogeneous aqueous solution;
(2) adding 0.30 part of curcumin into 22 parts of polypropylene glycol 1 by weight, and performing ultrasonic dispersion at 25 ℃ until the curcumin is fully dissolved, wherein the ultrasonic frequency is 40KHz, so as to obtain a curcumin polypropylene glycol solution;
(3) adding the curcumin polypropylene glycol solution obtained in the step (2) into the homogeneous phase aqueous solution obtained in the step (1), and magnetically stirring for 1h at 3 ℃ in an ice bath to form a uniformly dispersed emulsion; and introducing nitrogen flow into the emulsion for 30s to remove oxygen, then adding 0.27 part of ammonium persulfate and 0.18 part of N, N, N ', N' -tetramethyl ethylene diamine in sequence, keeping the stirring for 20min under the ice bath condition of 3 ℃ to uniformly mix, removing the ice bath and stirring magnetons, then pouring into a plastic mould, and carrying out sealed reaction for 12h at 25 ℃ in a dark place to obtain the curcumin-loaded polyacrylamide hydrogel dressing. The appearance was yellow and transparent, and was designated as gel 2. The pore diameter is distributed in the range of 1 to 100 μm, and the porosity is about 20%.
Example 3
(1) Dissolving 100 parts by weight of acrylamide and 0.48 part by weight of cross-linking agent N, N' -methylene bisacrylamide in 242 parts by weight of deionized water under the ice bath at the temperature of 3 ℃ through magnetic stirring to obtain a homogeneous phase aqueous solution;
(2) adding 0.38 part of curcumin into 58 parts of polypropylene glycol 2 by weight, and performing ultrasonic dispersion at 25 ℃ until the curcumin is fully dissolved, wherein the ultrasonic frequency is 40KHz, so as to obtain a curcumin polypropylene glycol solution;
(3) adding the curcumin polypropylene glycol solution obtained in the step (2) into the homogeneous phase aqueous solution obtained in the step (1), and magnetically stirring for 1.5 hours at the temperature of 3 ℃ in an ice bath to form a uniformly dispersed emulsion; and introducing nitrogen flow into the emulsion for 30s to remove oxygen, then adding 0.4 part of ammonium persulfate and 0.24 part of N, N, N ', N' -tetramethyl ethylene diamine in sequence, keeping the stirring for 10min under the ice bath condition of 3 ℃ to uniformly mix, removing the ice bath and stirring magnetons, then pouring into a plastic mould, and carrying out dark sealing reaction for 4h at 25 ℃ to obtain the curcumin-loaded polyacrylamide hydrogel dressing. The appearance was yellow and transparent, and was designated as gel 3. The pore diameter is distributed in 1-100 μm, and the porosity is about 60%.
Comparative example 1
Compared with the embodiment 1, the difference is that no curcumin is added, and the specific preparation steps are as follows:
according to parts by weight, 100 parts of acrylamide monomer and 0.06 part of cross-linking agent N, N' -methylene bisacrylamide are dissolved in 264 parts of deionized water under the condition of magnetic stirring at 3 ℃ in an ice bath to obtain homogeneous phase aqueous solution; then 36 parts of polypropylene glycol 1 is added, and the mixture is magnetically stirred for 2 hours under the ice bath condition of 3 ℃ to form evenly dispersed emulsion. And introducing nitrogen flow into the prepared emulsion for 30s to remove oxygen, then adding 0.18 part of ammonium persulfate and 0.12 part of N, N, N ', N' -tetramethyl ethylenediamine in sequence, keeping the mixture under an ice bath condition at 3 ℃, magnetically stirring for 20min, wherein the stirring speed in the whole preparation process is 600 revolutions per minute, removing the ice bath and stirring magnetons, pouring the mixed solution into a plastic mold, and carrying out light-proof sealing reaction for 24h at 25 ℃ to obtain the polyacrylamide hydrogel. The appearance was colorless and transparent, and was designated as comparative sample 1.
Comparative example 2
In comparison with example 1, the difference is that no polypropylene glycol is added. The preparation method comprises the following specific steps:
according to parts by weight, 100 parts of acrylamide monomer and 0.06 part of cross-linking agent N, N' -methylene bisacrylamide are dissolved in 264 parts of deionized water under the condition of magnetic stirring at 3 ℃ in an ice bath to obtain homogeneous phase aqueous solution; then 0.44 part of curcumin solid powder is added, and magnetic stirring is carried out for 2 hours under the ice bath condition of 3 ℃ to form suspension. And introducing nitrogen gas flow into the prepared suspension for 30s to remove oxygen, then adding 0.18 part of ammonium persulfate and 0.12 part of N, N, N ', N' -tetramethyl ethylenediamine in sequence, keeping the mixture under an ice bath condition at 3 ℃, magnetically stirring for 20min, wherein the stirring speed in the whole preparation process is 600 revolutions per minute, removing the ice bath and stirring magnetons, pouring the mixed solution into a plastic mold, and carrying out light-proof sealing reaction for 24h at 25 ℃ to obtain the polyacrylamide hydrogel. The appearance is light yellow and transparent, curcumin powder can be observed to be separated out on the surface of the hydrogel, and the sample is named as a comparative sample 2.
The performance test method comprises the following steps:
adhesion test: gel 1 samples were attached to the back of the hand, see fig. 2. It was observed that gel 1 formed good adhesion to the skin and did not readily fall off.
Flexibility and elasticity test: the sample is cut into strip samples with the length of about 40mm, the width of about 10mm and the thickness of about 2mm, the tensile property test of the sample is carried out on a universal material testing machine, the distance between clamps is 15 mm, the tensile rate is 100 mm/min, and the average value of five samples tested by each sample is taken. The test results are shown in FIG. 3.
The results show that the samples in examples 1-3 have tensile strength of more than 250KPa and elongation at break of more than 1400%, which indicates that the curcumin-loaded polyacrylamide hydrogel dressing has good flexibility and elasticity.
Curcumin loading test: selecting 420nm as curcumin detection wavelength, changing the concentration C of curcumin anhydrous ethanol solution by using a spectrophotometer, measuring the numerical value of absorbance A, and drawing a standard curve. The curcumin detection concentration is in a range of 1.06-5.28 mu g/mL, and the linear relation is good. Accurately weighing about 0.5g of polyacrylamide hydrogel sample loaded with curcumin, cutting the sample into tiny fragments, placing the fragments into a flask, adding 100ml of absolute ethyl alcohol, sealing, and ultrasonically shaking at 25 ℃ for 24h to extract the curcumin loaded in the polyacrylamide hydrogel as much as possible. And then centrifuging at 5000rpm for 5min, collecting supernatant, measuring the absorbance of the supernatant by using a spectrophotometer at a detection wavelength of 420nm, and calculating the load amount of curcumin in the polyacrylamide hydrogel. Three specimens were tested for each sample and the average calculated.
As a result of the test, the mean values of the curcumin loadings in gel 1, gel 2, gel 3 and comparative sample 2 were 824. mu.g/g, 530. mu.g/g, 667. mu.g/g and 108. mu.g/g, respectively. The load capacity of the curcumin of the gel 1, the gel 2 and the gel 3 is far higher than that of the comparative sample 2, which shows that the load capacity of the polyacrylamide hydrogel on the water-insoluble curcumin can be greatly improved by using the polypropylene glycol as the carrier of the curcumin.
Curcumin in vitro release test: phosphate buffered saline PBS containing 1% Tween 80 (pH = 7.2. about.7.4)As curcumin in vitro release buffer. Cutting the gel 1 into round sample pieces with diameter of about 25mm and thickness of about 2mm, and accurately weighingM 0(mass unit: g), soaked in 50mL release buffer, and tested for curcumin in vitro release at 37 ℃. 3mL of buffer solution was aspirated at regular intervals, and 3mL of fresh buffer solution was added and mixed well to continue the soaking. Diluting the buffer solution with appropriate amount of anhydrous ethanol (adjusting dilution ratio according to absorbance test result), measuring absorbance at 420nm wavelength, substituting into standard curve, calculating curcumin release amount, and recording asM i (i=1 to 10) (mass unit: μ g). And taking three sample test results to calculate an average value. Cumulative release rate of curcumin over extended sustained release time in gel 1 sampleR(%)。
Based on the average load capacity of the curcumin in the gel 1 of 824 mu g/g, the cumulative release rate of the curcumin along with the prolongation of the sustained release time is calculated according to the formula (1)R(%):
Figure 527249DEST_PATH_IMAGE001
The test results are shown in FIG. 4.
As shown by the test results in fig. 4, under the test conditions set in this experiment, the curcumin loaded on the gel 1 sample released faster in the initial 24 hours and then gradually slowed down, but the release rate still slowly increased until 120 hours. The polyacrylamide hydrogel dressing can slowly release curcumin for a long time and has long-term drug effect. The initial rapid release mainly comes from the release of curcumin loaded near the outer surface and the inner surface of the polyacrylamide hydrogel, and as the time is prolonged, the diffusion path of the curcumin from the inside of the hydrogel is lengthened, the difference between the internal concentration and the external concentration is reduced, and the release rate is slowed down.
And (3) microstructure testing: a fresh section of the sample was taken and the morphology was observed using an optical microscope, and the results of observation of gel 1, comparative sample 1 and comparative sample 2 are shown in FIG. 5.
Fig. 5A is an optical microscope photograph at 50 times magnification of the sample gel 1 before curcumin release, showing that there are many dark spherical droplets in the hydrogel in the field of view, i.e., polypropylene glycol droplets with dissolved curcumin;
FIG. 5B is a 50-fold magnified optical micrograph of the gel 1 sample after 120h of curcumin release testing, showing fewer dark colored spherical droplets in the hydrogel visible in the field of view, leaving a large number of light colored spherical droplets behind;
FIG. 5C is a 50-fold magnified optical micrograph of the sample of comparative sample 1 showing a large number of relatively uniform, light colored spherical droplets as polypropylene glycol without curcumin;
fig. 5D is an optical micrograph of the sample of comparative sample 2 at 50 x magnification, where no spherical droplets were observed and very little curcumin was found to adhere to the hydrogel surface.
The polypropylene glycol can exist in the polyacrylamide hydrogel in the form of spherical liquid drops, and the curcumin cannot be directly loaded on the polyacrylamide hydrogel, and can be stably loaded on the polyacrylamide hydrogel in the form of liquid drops by taking the polypropylene glycol as a medium. And the loaded curcumin can be released when in use.
And (3) fluorescence observation: curcumin is a natural compound with photosensitive property, can emit green fluorescence when being irradiated by ultraviolet rays, and polyacrylamide, water and polypropylene glycol have no autofluorescence, so that the loading condition of curcumin in a polyacrylamide gel sample can be observed by using a fluorescence microscope. Samples of gel 1 before and after curcumin release testing were photographed by observation using a fluorescence microscope, see fig. 6.
Fig. 6A is a fluorescence photograph magnified 5 times for the gel 1 sample loaded with curcumin (showing that the fluorescence part is curcumin), and fig. 6B is a fluorescence photograph magnified 5 times for the gel 1 sample after a curcumin release test for 120h, and it can be seen that curcumin is stably dispersed in the polyacrylamide hydrogel in the form of droplets, and most of the loaded curcumin can be released.
And (3) antibacterial property test: first 1 mL of bacterial suspension (bacterial concentration about 10)6cfu/ml) were leveled on nutrient agar plates and then different hydrogel samples were overlaidAfter incubation on the surface of the nutrient agar plate at 37 ℃ for a certain time interval, the nutrient agar plate was observed for the presence of a distinct zone of inhibition.
Gel 1 and comparison samples 1 and 2 are selected to carry out bacteriostasis tests and respectively correspond to sample 1, sample 2 and sample 3. The results of the experiment are shown in FIG. 7. As can be seen from FIGS. 7A and 7B, after 24h (1 day) of culture, neither control sample 1 nor control sample 2 had a significant zone of inhibition against E.coli and Staphylococcus aureus, indicating that neither control sample 1 nor control sample 2 had antibacterial activity against E.coli and Staphylococcus aureus; the gel 1 generates an inhibition zone of 8.9+5.1mm for escherichia coli and an inhibition zone of 9.3+6.2mm for staphylococcus aureus, and the polyacrylamide hydrogel dressing loaded with curcumin has obvious antibacterial activity for escherichia coli and staphylococcus aureus. As can be seen from FIGS. 7C and 7D, after 5 days of culture, the gel 1 sample still has a certain inhibitory effect on Escherichia coli and Staphylococcus aureus, which indicates that the polyacrylamide hydrogel dressing of the present invention has a long-acting antibacterial effect.

Claims (10)

1. The polyacrylamide hydrogel dressing is characterized by comprising the following components in parts by weight:
100 parts of acrylamide;
10-80 parts of polypropylene glycol;
0.02-1 part of a crosslinking agent;
0.1-1 part of redox initiator;
0.2-1 part of curcumin;
220-290 parts of water;
wherein the redox initiator comprises 0.05-0.70 parts of oxidant and 0.05-0.30 parts of reducing agent;
the preparation method of the polyacrylamide hydrogel dressing comprises the following steps:
(1) according to the proportion, acrylamide and a cross-linking agent are dissolved in water under the condition of ice bath at 0-5 ℃ by stirring to obtain a homogeneous phase aqueous solution;
(2) adding curcumin into polypropylene glycol according to a ratio, and performing ultrasonic dispersion at the temperature of 20-30 ℃ until the curcumin is fully dissolved, wherein the ultrasonic frequency is 25-80 KHz, so as to obtain a curcumin polypropylene glycol solution;
(3) adding the curcumin polypropylene glycol solution obtained in the step (2) into the homogeneous phase aqueous solution obtained in the step (1), and stirring for 0.5-2 hours at an ice bath temperature of 0-5 ℃ to form a uniformly dispersed emulsion; and introducing nitrogen flow into the emulsion for 30-60 s to remove oxygen, adding a redox initiator, continuously stirring for 10-30 min at the temperature of 0-5 ℃ in an ice bath to uniformly mix, and then sealing in the dark at the temperature of 20-30 ℃ to perform polymerization reaction for 4-24 h to obtain the curcumin-loaded polyacrylamide hydrogel dressing.
2. The polyacrylamide hydrogel dressing of claim 1, characterized by comprising the following components in parts by weight:
100 parts of acrylamide;
20-60 parts of polypropylene glycol;
0.03-0.5 part of a crosslinking agent;
0.25-0.7 parts of redox initiator;
0.30-0.75 parts of curcumin;
250-270 parts of water;
wherein the redox initiator comprises 0.15-0.45 part of oxidant and 0.10-0.25 part of reducing agent.
3. The polyacrylamide hydrogel dressing of claim 1, wherein the polyacrylamide hydrogel dressing has a pore structure with pore size distribution of 1-10 μm and porosity of 20-60%; the load capacity of curcumin of the polyacrylamide hydrogel dressing is 500-1000 mug/g.
4. The polyacrylamide hydrogel dressing of claim 1 wherein the polypropylene glycol has a number average molecular weight of 200 to 4000; the cross-linking agent is selected from any one of N, N' -methylene bisacrylamide or ethylene glycol dimethacrylate; the oxidant is selected from any one of persulfate, chlorate or ammonium ceric nitrate; the reducing agent is selected from any one of N, N, N ', N' -tetramethyl ethylenediamine, sodium sulfite or thiourea.
5. The polyacrylamide hydrogel dressing of claim 4 wherein the redox initiator is selected from any one of ammonium persulfate/N, N, N ', N' -tetramethylethylenediamine, potassium persulfate/N, N, N ', N' -tetramethylethylenediamine, ammonium persulfate/sodium sulfite, potassium persulfate/sodium sulfite, sodium chlorate/sodium sulfite, or ceric ammonium nitrate/thiourea.
6. The polyacrylamide hydrogel dressing of claim 1 wherein said water is deionized water.
7. The polyacrylamide hydrogel dressing of claim 1 wherein magnetic stirring is used for said stirring, and the speed of said magnetic stirring is 500-1000 rpm.
8. The polyacrylamide hydrogel dressing of claim 1 wherein the polymerization reaction in step (3) is carried out in a plastic mold.
9. The polyacrylamide hydrogel dressing of claim 3 wherein said polyacrylamide hydrogel dressing has a spherical pore structure.
10. Use of the polyacrylamide hydrogel dressing of any one of claims 1 to 9 for traumatic, burn, scald, ulcer or decubitus wounds.
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