Hydrogel fiber loaded with curcumin nanoparticles and preparation method thereof

Abstract

The invention discloses hydrogel fibers loaded with curcumin nanoparticles and a preparation method of the hydrogel fibers, and belongs to the field of functional fibers. According to the preparation method disclosed by the invention, the dopamine is added, and the curcumin and the dopamine are combined and self-assembled into the curcumin nano-particle self-polymer through an oxidation self-polymerization reaction of the dopamine under an alkaline condition, so that the specific surface area of the curcumin is increased, and the hydrophilicity and the drug activity of the curcumin are improved; and the hydrogel fiber loaded with the curcumin nanoparticles is prepared by a wet spinning technology. The hydrogel fiber loaded with the curcumin nanoparticles prepared by the invention has a natural structure and various excellent properties such as good biocompatibility and controllable biodegradability, and has important scientific research value and practical significance in the field of biomedical materials.

Description

Technical Field

[0001] The invention relates to a hydrogel fiber loaded with curcumin nanoparticles and a preparation method thereof, belonging to the field of functional fibers. Background Art

[0002] Hydrogel fibers differ significantly from traditional polymer fibers in many aspects. Hydrogel fibers are fibers with high water content, and their core feature is that they can absorb and release large amounts of water while maintaining their structure in water. Hydrogel fibers have both the performance characteristics of hydrogels and the structural advantages of fiber materials, and are good drug delivery platforms; the high specific surface area of ​​hydrogel fibers gives them better hygroscopicity, moisture retention, and breathability, and they can simulate the microfiber structure of human tissues by regulating their size, such as nerve cells, muscle fibers, tendons, ligaments, and other tissues; hydrogel fibers can also be prepared into textile materials through knitting, weaving, braiding, non-woven and other textile processing technologies for use in the biomedical field.

[0003] Hydrogel fibers are usually prepared by wet spinning or electrospinning technology, and different spinning technologies have different requirements for spinning solutions. Wet spinning is a process in which fiber-forming polymers are dissolved in an appropriate solvent and passed through a spinneret into a coagulation bath to form fibers. There are specific requirements for the concentration, viscosity and flow characteristics of the spinning solution to ensure that uniform fibers can be formed in the coagulation bath; electrospinning is a technology that uses electrostatic force as a traction force to prepare nanofibers. Its requirements for the spinning solution include appropriate viscosity, surface tension and conductivity, which affect the morphology and performance of the fiber.

[0004] Curcumin (Cur) is a bioactive pigment extracted from the ginger root plant. It is a natural hydrophobic polyphenol compound. Curcumin has antioxidant, anticoagulant, anti-inflammatory, antitumor, antibacterial, antiviral and other drug activities, and has been shown to have good wound healing activity; however, the natural flavonoid curcumin is unstable, hydrophobic, and has extremely poor solubility, making it difficult to exert its drug activity, degrades quickly, and has extremely low bioavailability, which limits its clinical application.

[0005] There are many ways to improve the performance of curcumin in current research, such as:

[0006] Patent CN 116270477 A discloses an amorphous curcumin nanoparticle and its preparation method and application. The method needs to add a lyophilization protective agent to preserve the prepared curcumin nanoparticles for lyophilization. The above preparation method is relatively costly and is not suitable for low-cost mass production of curcumin nanoparticles.

[0007] Patent CN 116459387 A discloses an antibacterial, anti-inflammatory and healing-promoting hydrogel dressing and a preparation method thereof. The hydrogel dressing prepared by the method loads curcumin by electrospinning nanofibers; however, the coagulation liquid used in electrospinning is mostly an organic solvent, which is very harmful and not suitable for use in the biomedical field; the solution requires a long solidification time and the production speed is slow; and the operation process involves high voltage, which places higher requirements on the equipment, making electrospinning more complicated and costly in the industrial process;

[0008] Patent CN 105040137 B discloses a method for preparing curcumin-loaded polyacrylonitrile fibers by a stock solution coloring method. The spinning solution composed of polyacrylonitrile, curcumin, a transdermal absorption enhancer and a solvent can be used to prepare colored fibers by a wet spinning process, a dry spinning process or a dry-jet wet spinning process. The spinning stock solution used is polyacrylonitrile, and a drug transdermal absorption enhancer, a solvent and a coagulation bath must be used, most of which are toxic organic solvents, making it difficult to ensure that the spinning process is safe and non-toxic.

[0009] Therefore, it is necessary to use green and non-toxic reagents to prepare a hydrogel fiber loaded with curcumin nanoparticles to improve the hydrophilicity and drug activity of curcumin, and prepare it into a textile material by a wet spinning method for application in the biomedical field. Summary of the invention

[0010] [Technical issues]

[0011] Curcumin has problems such as poor water solubility, instability and low bioavailability. It is difficult to exert its pharmaceutical activity when loaded into hydrogel fibers through wet spinning technology.

[0012] [Technical solution]

[0013] In order to solve the above problems, the present invention combines curcumin with dopamine through the oxidative self-polymerization reaction of dopamine under alkaline conditions, and self-assembles into curcumin nanoparticle self-polymers, thereby improving the specific surface area of ​​curcumin, increasing the hydrophilicity and pharmaceutical activity of curcumin; and preparing hydrogel fibers loaded with curcumin nanoparticles through wet spinning technology.

[0014] The first object of the present invention is to provide a method for preparing hydrogel fibers loaded with curcumin nanoparticles, comprising the following steps:

[0015] (1) dissolving curcumin and dopamine hydrochloride in an ethanol aqueous solution, adjusting the pH to 7-8, and continuing to mix to obtain a mixture; evaporating and drying the mixture to obtain curcumin nanoparticles;

[0016] (2) mixing the curcumin nanoparticles and the sodium alginate aqueous solution to obtain a spinning solution;

[0017] (3) The spinning solution is prepared by wet spinning to obtain curcumin nanoparticle hydrogel fibers.

[0018] As an embodiment of the present invention, in step (1), the mass ratio of curcumin to dopamine hydrochloride is 0.05-1g:0.01-1g, preferably 0.05g:0.1g.

[0019] As an embodiment of the present invention, the volume fraction of the ethanol aqueous solution in step (1) is 20-80%, preferably 60%.

[0020] As an embodiment of the present invention, in step (1), the usage ratio of curcumin and ethanol aqueous solution is 0.01-1 g:40 mL.

[0021] As an embodiment of the present invention, in step (1), the pH is adjusted by using an alkaline reagent, which is one of an aqueous solution of ammonium hydroxide and ammonia water, preferably ammonia water, with a mass concentration of 25%.

[0022] As an embodiment of the present invention, the continued mixing in step (1) is achieved by magnetic stirring; the magnetic stirring is carried out at 200 to 800 rpm for 2 to 24 hours, preferably 12 hours.

[0023] As an embodiment of the present invention, the evaporation in step (1) is rotary evaporation, specifically rotary evaporation at 20-40° C. for 20-30 min.

[0024] As an embodiment of the present invention, the mass concentration of the sodium alginate aqueous solution in step (2) is 1-5%.

[0025] As an embodiment of the present invention, in step (2), the concentration of curcumin nanoparticles in the sodium alginate aqueous solution is 0.1-0.4 μg / mL, preferably 0.25 μg / mL.

[0026] As an embodiment of the present invention, the uniform mixing in step (2) is achieved by ultrasound or stirring; ultrasound is performed at 200-400W for 3-8min, and stirring is performed at 200-800rpm for 5-15min.

[0027] As an embodiment of the present invention, the coagulation bath used in the wet spinning in step (3) is a calcium chloride aqueous solution with a mass concentration of 1 to 5%, preferably a calcium chloride aqueous solution with a mass concentration of 3%.

[0028] As an embodiment of the present invention, the wet spinning in step (3) adopts a flexible drawing spinning platform, the extrusion speed of the spinning solution is 0.1 to 5 mL / min, the fluid circulation speed is 0.42 to 3 m / s, and the inner diameter of the injection needle is 0.16 to 3.3 mm.

[0029] The second object of the present invention is the hydrogel fiber loaded with curcumin nanoparticles prepared by the method according to the present invention.

[0030] As an embodiment of the present invention, the particle size of the curcumin nanoparticles is between 100 nm and 320 nm, and the PDI is between 0.15 and 0.3.

[0031] As an embodiment of the present invention, the diameter of the hydrogel fiber loaded with curcumin nanoparticles is 30 μm to 50 μm.

[0032] The third object of the present invention is to use the hydrogel fiber loaded with curcumin nanoparticles in the field of functional textile materials or biomedicine.

[0033] The fourth object of the present invention is to provide a wound dressing, which uses the hydrogel fiber loaded with curcumin nanoparticles of the present invention.

[0034] A fifth object of the present invention is to provide a fabric, which is woven using the hydrogel fibers loaded with curcumin nanoparticles according to the present invention.

[0035] The sixth object of the present invention is a method for improving the bioavailability of curcumin, which uses the hydrogel fiber loaded with curcumin nanoparticles of the present invention.

[0036] [Beneficial Effects]

[0037] (1) The preparation method of the present invention is green and environmentally friendly, has low production cost, does not use toxic and harmful reagents, and is more suitable for the biomedical field.

[0038] (2) The preparation method of the curcumin nanoparticles and the hydrogel fibers loaded with curcumin nanoparticles in the present invention is simple to operate, and the instruments required in the preparation process are suitable for mass production of drug-loaded hydrogel fibers in factories.

[0039] (3) The curcumin nanoparticles prepared by the present invention have uniform morphology and size, good dispersibility and good hydrophilicity.

[0040] (4) The hydrogel fibers loaded with curcumin nanoparticles prepared by the present invention have a natural structure, as well as multiple excellent properties such as good biocompatibility and controllable biodegradability, and have important scientific research value and practical significance in the field of biomedical materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 This is a scanning electron microscope image of the curcumin nanoparticles prepared in Example 1.

[0042] Figure 2 This is a particle size analysis diagram of curcumin nanoparticles prepared in Example 1.

[0043] Figure 3 This is the infrared spectrum of the curcumin nanoparticles prepared in Example 1.

[0044] Figure 4 This is a scanning electron micrograph of the curcumin nanoparticle-loaded hydrogel fiber prepared in Example 1.

[0045] Figure 5 This is a scanning electron microscope image of the curcumin nanoparticles prepared in Example 2.

[0046] Figure 6 This is an analysis diagram of the antioxidant activity of the curcumin nanoparticle-loaded hydrogel fiber prepared in Example 3.

[0047] Figure 7 This is a diagram for analyzing the hemolytic performance of the curcumin nanoparticle-loaded hydrogel fiber prepared in Example 3.

[0048] Figure 8 This is a scanning electron micrograph of curcumin nanoparticles prepared in Comparative Example 1. DETAILED DESCRIPTION

[0049] The preferred embodiments of the present invention are described below. It should be understood that the embodiments are for better explaining the present invention and are not used to limit the present invention.

[0050] Test method:

[0051] 1. Particle size analysis:

[0052] Curcumin nanoparticles were dispersed in ethanol, diluted to an appropriate concentration, and dispersed evenly by ultrasound. The particle size and polydispersity index (PDI) of Cur nanoparticles were measured at 25°C using a nanoparticle size analyzer with dynamic light scattering (DLS).

[0053] 2. Antioxidant activity test:

[0054] Dissolve 3 mg ABTS in 1.43 mL deionized water and 1 mg potassium persulfate in 0.735 mL deionized water, mix the above solutions to oxidize them to generate ABTS free radicals. Keep it away from light and let it stand at room temperature for 12 hours. Dilute ABTS with PBS hydrochloric acid buffer to a suitable concentration, usually with an absorbance of about 0.7 at 734 nm. Take 1 mL of the prepared ABTS solution and add it dropwise to 5 mg of the sample. After 5 minutes at room temperature away from light, use an ELISA reader to test the absorbance at 734 nm.

[0055] 3. Hemolytic performance test:

[0056] Weigh 2 mg of sample and place it in a centrifuge tube, then add 800 μL of PBS to 200 μL of red blood cell suspension and incubate in a 37°C incubator for 1 hour. After the sample is incubated in a 37°C incubator for 1 hour, centrifuge at 5000 rpm for 5 minutes, aspirate the supernatant, and measure the absorbance of the supernatant at 540 nm using an ELISA reader.

[0057] 4. Mechanical properties test:

[0058] The fiber strength is measured by a fiber gauge.

[0059] 5. Solubility test:

[0060] Take a certain amount of curcumin and dissolve it in water to ensure that it is completely dissolved; then take a certain amount and measure the absorbance at 427nm using an ultraviolet spectrophotometer; use curcumin solutions of different concentrations for testing and fit them to make a standard curve;

[0061] Dissolve 0.5g of curcumin in 100g of water to ensure complete dissolution; test the absorbance at 427nm and insert it into the standard curve to obtain the actual concentration;

[0062] Dissolve 0.5 g of curcumin nanoparticles in 100 g of water to ensure complete dissolution; test the absorbance at 427 nm and bring it into the standard curve to obtain the actual concentration.

[0063] The raw materials used in the embodiment:

[0064] Ammonia water, curcumin, dopamine hydrochloride, sodium alginate and the like are all commercially available.

[0065] The % involved in the examples without specific meaning refers to mass percentage, the solution involved without specific solvent is water as the solvent; the reaction temperature not mentioned is room temperature reaction, and room temperature refers to 20-30°C.

[0066] Example 1

[0067] A method for preparing hydrogel fibers loaded with curcumin nanoparticles comprises the following steps:

[0068] (1) 0.05 g of curcumin and 0.1 g of dopamine hydrochloride were dissolved in 40 mL of 60% ethanol aqueous solution, and the pH of the system was adjusted to 7.5 by 25% ammonia aqueous solution; then, the mixture was magnetically stirred at 600 rpm for 12 h to obtain a mixture; the mixture was rotary evaporated at 40° C. for 30 min and dried to obtain curcumin nanoparticles;

[0069] (2) adding curcumin nanoparticles to a sodium alginate aqueous solution with a mass concentration of 2%, and ultrasonicating at 300 W for 5 min to obtain a spinning solution; wherein the concentration of the curcumin nanoparticles in the sodium alginate aqueous solution is 0.25 μg / mL;

[0070] (3) A 3% calcium chloride solution was used as a coagulation bath for wet spinning to prepare curcumin nanoparticle hydrogel fibers (fineness of 33 μm) by wet spinning; wherein the wet spinning adopted a flexible drawing spinning platform, the spinning solution was spun through a syringe with a needle inner diameter of 0.21 mm, the propulsion speed was 0.8 min / mL, and the fluid circulation speed was 1.32 m / s.

[0071] The obtained curcumin nanoparticles and hydrogel fibers were subjected to performance tests, and the test results are as follows:

[0072] (1) Scanning electron microscopy images of curcumin nanoparticles Figure 1 .

[0073] from Figure 1 It can be seen that the particle size of the synthesized curcumin nanoparticles is uniform.

[0074] (2) Particle size analysis of curcumin nanoparticles Figure 2 .

[0075] from Figure 2 It can be seen that the particle size of curcumin nanoparticles is 303 nm and the PDI is 0.25.

[0076] (3) Infrared analysis of curcumin nanoparticles Figure 3 .

[0077] from Figure 3 It can be seen that the FTIR spectrum of curcumin nanoparticles is at 1629 cm -1 Up to 1508cm -1 The absorption peaks in the range are attributed to the double bond vibration of the Cur carbonyl benzene ring C=O and the phenolic hydroxyl C=C, at 1281 cm -1 The absorption peak is caused by Ar-O stretching vibration. The above data show that PDA is successfully coated on the surface of curcumin to form PDA-Cur nanoparticles with uniform size.

[0078] (4) SEM images of hydrogel fibers Figure 4 .

[0079] from Figure 4 It can be seen that the prepared hydrogel fibers have uniform fineness.

[0080] (5) Mechanical properties test:

[0081] The strength of the hydrogel fiber is 20Mpa-25Mpa, and the elongation at break is 85%-100%; compared with the mechanical properties of the hydrogel fiber without the addition of curcumin nanoparticles, there is no change.

[0082] Example 2 Optimization of the mass ratio of curcumin to dopamine hydrochloride

[0083] The mass of curcumin in step (1) of Example 1 was adjusted to 0 g, 0.05 g, and 0.1 g, and the mass of dopamine hydrochloride was adjusted to 0.2 g, so that the mass ratio of curcumin to dopamine hydrochloride was 0%, 25%, and 50%, and the rest was kept consistent with Example 1, to obtain curcumin nanoparticles.

[0084] The obtained curcumin nanoparticles were subjected to performance tests, and the test results are as follows:

[0085] Scanning electron microscopy images of curcumin nanoparticles Figure 5 ,from Figure 5 It can be seen that the particle size of curcumin nanoparticles increases from 170nm to 306nm. This shows that the content of curcumin has a certain influence on the formation of curcumin-dopamine nanoparticles. When the curcumin content is low, it is difficult to observe curcumin attached to the dopamine surface through scanning electron microscopy. When the curcumin concentration is high, the particle size of the synthesized nanoparticles is uneven, and it is difficult to achieve uniform loading in the hydrogel fiber.

[0086] Example 3 Optimization of curcumin nanoparticle content

[0087] The concentration of the curcumin nanoparticles in the sodium alginate aqueous solution in Example 1 was adjusted to 0 μg / mL, 0.25 μg / mL, 0.5 μg / mL, 1 μg / mL, and 2 μg / mL, and other parameters remained unchanged to obtain hydrogel fibers with different loading amounts.

[0088] The obtained hydrogel fiber was subjected to performance testing, and the test results are as follows:

[0089] According to the provisions of ISO 10993-4, a hemolysis rate of less than 5% is considered to have good blood compatibility. The hemolysis performance of the hydrogel fiber loaded with curcumin nanoparticles was tested by in vitro solution. Figure 6 .from Figure 6It can be seen that the hemolysis rate of DDW (deionized water) is 100%, the hemolysis rate of COTTON (cotton gauze) is 1.6%, the hemolysis rate of 0 μg / mL is 1%, the hemolysis rate of 0.25 μg / mL is 0.56%, the hemolysis rate of 0.5 μg / mL is 0.82%, the hemolysis rate of 1 μg / mL is 1.11%, and the hemolysis rate of 2 μg / mL is 1.34%; the hemolysis rates of all hydrogel fibers are less than 5%, which indicates that the hydrogel fibers have good blood compatibility.

[0090] A good wound material should have a certain ability to scavenge free radicals. The antioxidant activity of hydrogel fibers loaded with curcumin nanoparticles was tested by the ABTS method. Figure 7 .from Figure 7 It can be seen that the ABTS free radical scavenging rate at a concentration of 0 μg / mL is 54.6%, the ABTS free radical scavenging rate at a concentration of 0.25 μg / mL is 73.9%, the ABTS free radical scavenging rate at a concentration of 0.5 μg / mL is 88.2%, the ABTS free radical scavenging rate at a concentration of 1 μg / mL is 88.56%, and the ABTS free radical scavenging rate at a concentration of 2 μg / mL is 90.1%. With the increase of the content of curcumin nanoparticles, the free radical scavenging rate of the hydrogel fiber is also increasing, indicating that the sample loaded with curcumin nanoparticles has good antioxidant activity. And when the content of curcumin nanoparticles increases to 0.5 μg / mL, the growth rate of its ABTS free radical scavenging rate (%) decreases.

[0091] When the concentration of curcumin nanoparticles in sodium alginate aqueous solution is 0.5 μg / mL, the solubility is 40%; and the solubility of curcumin itself is 9%; it can be seen that the formation of curcumin nanoparticles can greatly improve its solubility.

[0092] Comparative Example 1

[0093] A method for preparing hydrogel fibers loaded with curcumin nanoparticles comprises the following steps:

[0094] (1) 0.01 g of curcumin and 0.1 g of dopamine hydrochloride were dissolved in 40 mL of 60% ethanol aqueous solution, and the pH of the system was adjusted to 7.5 by 25% ammonia aqueous solution; then, the mixture was magnetically stirred at 200 rpm for 2 h to obtain a mixture; the mixture was rotary evaporated at 40° C. for 30 min and dried to obtain curcumin nanoparticles;

[0095] (2) adding curcumin nanoparticles to a sodium alginate aqueous solution with a mass concentration of 2%, and ultrasonicating at 300 W for 5 min to obtain a spinning solution; wherein the concentration of the curcumin nanoparticles in the sodium alginate aqueous solution is 0.25 μg / mL;

[0096] (3) A 3% calcium chloride solution was used as a coagulation bath for wet spinning to prepare curcumin nanoparticle hydrogel fibers (fineness 33 μm) by wet spinning; wherein the wet spinning adopted a flexible drawing spinning platform, the spinning solution was spun through a syringe with a needle inner diameter of 0.21 mm, the propulsion speed was 0.8 min / mL, and the fluid circulation speed was 1.32 m / s.

[0097] The obtained curcumin nanoparticles and hydrogel fibers were subjected to performance tests, and the test results are as follows:

[0098] Scanning electron microscopy images of curcumin nanoparticles Figure 8 .from Figure 8 It can be seen that the surface of the synthesized curcumin nanoparticles is smooth, indicating that curcumin is not successfully loaded on the dopamine nanoparticles, indicating that the curcumin nanoparticles are not successfully prepared.

[0099] Although the present invention has been disclosed as above in the form of a preferred embodiment, it is not intended to limit the present invention. Anyone familiar with this technology can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be based on the definition of the claims.

Claims

1. A method for preparing hydrogel fibers loaded with curcumin nanoparticles, characterized in that: The steps include: (1) dissolving curcumin and dopamine hydrochloride in an ethanol aqueous solution, adjusting the pH to 7-8, and continuing to mix to obtain a mixture; evaporating and drying the mixture to obtain curcumin nanoparticles; (2) mixing the curcumin nanoparticles and the sodium alginate aqueous solution to obtain a spinning solution; (3) The spinning solution is prepared by wet spinning to obtain curcumin nanoparticle hydrogel fibers.

2. The method according to claim 1, characterized in that In step (1), the mass ratio of curcumin to dopamine hydrochloride is 0.05-1 g: 0.01-1 g.

3. The method according to claim 1, characterized in that: In step (1), the usage ratio of curcumin and ethanol aqueous solution is 0.01-1 g:40 mL.

4. The method according to claim 1, characterized in that In step (2), the concentration of curcumin nanoparticles in the sodium alginate aqueous solution is 0.1-0.4 μg / mL.

5. The method according to claim 1, characterized in that The wet spinning in step (3) adopts a flexible drawing spinning platform, the extrusion speed of the spinning solution is 0.1-5 mL / min, the fluid circulation speed is 0.42-3 m / s, and the inner diameter of the injection needle is 0.16-3.3 mm.

6. The hydrogel fiber loaded with curcumin nanoparticles prepared by the method according to any one of claims 1 to 5.

7. Application of the hydrogel fiber loaded with curcumin nanoparticles according to claim 6 in the field of functional textile materials or biomedicine.

8. A wound dressing, characterized in that: It adopts the hydrogel fiber loaded with curcumin nanoparticles as claimed in claim 6.

9. A fabric, characterized in that: It adopts the hydrogel fiber loaded with curcumin nanoparticles as claimed in claim 6.

10. A method for improving the bioavailability of curcumin, characterized in that: It adopts the hydrogel fiber loaded with curcumin nanoparticles as claimed in claim 6.

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