Carrying 4apos; preparation method and application of nanofiber hydrogel of-hydroxychalcone

Abstract

The invention relates to the technical field of biomedical materials and wound repair, and discloses a preparation method and application of 4 '-hydroxychalcone-loaded nanofiber hydrogel, the preparation method comprises the following steps: mixing 4'-hydroxychalcone and polylactic acid according to a mass ratio of 1: (6-12), and carrying out ultrasonic treatment to obtain 4 '-hydroxychalcone-loaded nanofiber hydrogel; preparing nanofibers containing 4 '-hydroxychalcone by adopting an electrostatic spinning technology; according to the present invention, the 4 '-hydroxychalcone-loaded nanofiber hydrogel has the following characteristics that the drug in the 4'-hydroxychalcone-loaded nanofiber hydrogel can be continuously released, and the cumulative release rate can achieve 70-85% within 72 h so as to maintain the stable drug action concentration on the wound surface; meanwhile, the nanofiber hydrogel has good water retention capacity, the water retention rate of the nanofiber hydrogel can reach 90-95%, a stable wet healing environment can be provided for the wound surface, and the wound surface repairing process is facilitated.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials and wound repair technology, and in particular to the preparation method and application of nanofiber hydrogels loaded with 4'-hydroxychalcone. Background Technology

[0002] Due to their unique pathological microenvironment, diabetic wounds often exhibit persistent inflammation and decreased tissue repair capacity, making it difficult for the wounds to heal quickly and leading to chronic diabetic wounds. These wounds typically fail to heal for a long time, significantly impacting patients' quality of life and health.

[0003] Currently, treatments for chronic diabetic wounds mainly include antibiotic therapy, debridement, and application of dry dressings such as gauze. However, these treatments have limitations in practical application and cannot fully address the difficulty in healing chronic diabetic wounds. Therefore, there is an urgent need for a treatment method that can overcome the adverse effects of the diabetic pathological microenvironment to effectively promote the healing of chronic diabetic wounds.

[0004] Specifically, antibiotic treatment can easily lead to drug resistance with long-term use, affecting the treatment effect; growth factor therapy, due to its small molecular weight and short half-life, is difficult to maintain an effective concentration at the wound site for a long time, thus limiting its sustained efficacy; and debridement or covering with dry dressings such as gauze can easily cause secondary damage to the wound, which is not conducive to the wound repair process. Summary of the Invention

[0005] The purpose of this invention is to address the shortcomings of existing technologies by proposing a method for preparing and applying nanofiber hydrogels loaded with 4'-hydroxychalcone.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] A method for preparing nanofiber hydrogels loaded with 4'-hydroxychalcone includes the following steps:

[0008] Step 1: Mix 4′-hydroxychalcone and polylactic acid at a mass ratio of 1:(6-12), and prepare nanofibers containing 4′-hydroxychalcone using electrospinning technology;

[0009] Step 2: Homogenize the nanofibers to form short fibers;

[0010] Step 3: The short fibers are uniformly mixed into a hydrogel matrix composed of polyvinyl alcohol and high molecular weight hyaluronic acid;

[0011] Step 4: Perform freeze-thaw cycles on the mixed hydrogel to obtain a nanofiber hydrogel loaded with 4′-hydroxychalcone.

[0012] Preferably, in step 1, 4′-hydroxychalcone and polylactic acid are mixed at a mass ratio of 1:10.

[0013] Preferably, in the hydrogel matrix of step 3, the mass ratio of polyvinyl alcohol to high molecular weight hyaluronic acid is (6-10):1.

[0014] Preferably, in the hydrogel matrix of step 3, the mass ratio of polyvinyl alcohol to high molecular weight hyaluronic acid is 8:1.

[0015] Preferably, the freeze-thaw cycle in step 4 includes freezing at −20°C for 20-24 hours and then thawing at 25°C for 1-4 hours.

[0016] Preferably, the freeze-thaw cycle in step 4 includes freezing at −20°C for 22 hours and then thawing at 25°C for 2 hours.

[0017] The nanofiber hydrogel loaded with 4'-hydroxychalcone was prepared by the above-described method.

[0018] The above-mentioned nanofiber hydrogels carrying 4'-hydroxychalcone are used in drugs that promote the healing of chronic diabetic wounds.

[0019] The beneficial effects of this invention are as follows:

[0020] The 4′-hydroxychalcone-loaded nanofiber hydrogel provided by this invention enables continuous drug release, with a cumulative release rate of 70-85% within 72 hours, thus maintaining a relatively stable drug concentration at the wound site. At the same time, the nanofiber hydrogel has good water retention properties, with a water retention rate of 90-95%, which can provide a stable moist healing environment for the wound and facilitate the wound repair process.

[0021] Furthermore, the nanofiber hydrogel carrying 4′-hydroxychalcone not only provides a moist healing environment but also exerts multi-target biological effects through the slow release of 4′-hydroxychalcone, allowing the drug to exert its effects at the wound site for a prolonged period, thereby synergistically promoting the healing of chronic diabetic wounds. Through the above methods, the nanofiber hydrogel of this invention can more effectively promote wound repair, and its preparation method lays the foundation for subsequent related research and applications. Attached Figure Description

[0022] Figure 1 Comparison of healing status of diabetic wounds in mice under different treatment conditions at different time points;

[0023] Figure 2 This figure shows a comparison of the changes in the area of ​​diabetic lesions in mice under different treatment conditions over time. Detailed Implementation

[0024] To provide a clearer understanding of the technical features, objectives, and beneficial effects of this invention, the technical solution of this invention is described in detail below, but this should not be construed as limiting the scope of implementation of this invention. Unless otherwise specified, the methods used in this invention are conventional methods in this technical field. In this invention, materials, reagents, or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.

[0025] In one embodiment, the present invention provides a method for preparing nanofiber hydrogels loaded with 4'-hydroxychalcone, comprising the following steps:

[0026] Step 1: Mix 4′-hydroxychalcone and polylactic acid at a mass ratio of 1:(6-12), and prepare nanofibers containing 4′-hydroxychalcone using electrospinning technology;

[0027] Step 2: Homogenize the nanofibers to form short fibers;

[0028] Step 3: The short fibers are uniformly mixed into a hydrogel matrix composed of polyvinyl alcohol and high molecular weight hyaluronic acid;

[0029] Step 4: Perform freeze-thaw cycles on the mixed hydrogel to obtain a nanofiber hydrogel loaded with 4′-hydroxychalcone.

[0030] In a preferred embodiment of the present invention, in step 1, 4′-hydroxychalcone and polylactic acid are mixed at a mass ratio of 1:10.

[0031] In a preferred embodiment of the present invention, in the hydrogel matrix of step 3, the mass ratio of polyvinyl alcohol to high molecular weight hyaluronic acid is (6-10):1.

[0032] In a preferred embodiment of the present invention, in the hydrogel matrix of step 3, the mass ratio of polyvinyl alcohol to high molecular weight hyaluronic acid is 8:1.

[0033] As a preferred embodiment of the present invention, the freeze-thaw cycle treatment in step 4 includes freezing at −20°C for 20-24 hours and thawing at 25°C for 1-4 hours.

[0034] As a preferred embodiment of the present invention, the freeze-thaw cycle treatment in step 4 includes freezing at −20°C for 22 hours and then thawing at 25°C for 2 hours.

[0035] In one embodiment, the present invention also provides a nanofiber hydrogel loaded with 4'-hydroxychalcone, prepared by the above-described preparation method.

[0036] In one embodiment, the present invention also proposes the use of the above-described nanofiber hydrogel loaded with 4'-hydroxychalcone in a drug for promoting the healing of chronic diabetic wounds.

[0037] The specific implementation of the present invention will be described in detail below with reference to specific embodiments.

[0038] Example 1: 4′-hydroxychalcone and polylactic acid were mixed at a mass ratio of 1:(6-12), and nanofibers containing 4′-hydroxychalcone were prepared by electrospinning. The nanofibers were homogenized to form short fibers. The short fibers were uniformly mixed into a hydrogel matrix composed of polyvinyl alcohol and high molecular weight hyaluronic acid, wherein the mass ratio of polyvinyl alcohol to high molecular weight hyaluronic acid in the hydrogel matrix was (6-10):1. The mixed hydrogel was frozen at −20°C for 20-24 hours and then thawed at 25°C for 1-4 hours to obtain the nanofiber hydrogel carrying 4′-hydroxychalcone.

[0039] Test Example 1: An animal experiment was conducted to evaluate the effect of 4′-hydroxychalcone-loaded nanofiber hydrogels on promoting the healing of chronic diabetic wounds. Six groups were set up for the animal experiment: a diabetic model control group, a nanofiber hydrogel group without 4′-hydroxychalcone, a nanofiber hydrogel group containing a low dose of 4′-hydroxychalcone, a nanofiber hydrogel group containing a high dose of 4′-hydroxychalcone, a positive control group, and a non-diabetic normal mouse control group. Eight mice were included in each group, and each group received the corresponding treatment.

[0040] Wound healing experiments were conducted using a type 2 diabetic mouse model. During the experiment, nanofiber hydrogels without 4′-hydroxychalcone, nanofiber hydrogels containing high and low doses of 4′-hydroxychalcone, and a positive control drug were applied to the wound surfaces of different groups of mice. The low dose was 1.5 mg / mL, and the high dose was 3 mg / mL. Mice in each group received the corresponding treatment, and the wounds were photographed and observed on days 0, 3, 6, 9, and 12. Figure 1 As shown, by recording and analyzing changes in the wound, the promoting effect of nanofiber hydrogels carrying 4′-hydroxychalcone on wound healing was evaluated.

[0041] Experimental results are as follows Figure 1 and Figure 2As shown, compared with the control group, mice treated with nanofiber hydrogels loaded with 4′-hydroxychalcone experienced significantly faster wound healing. Furthermore, the high-dose 4′-hydroxychalcone nanofiber hydrogel group exhibited significantly better wound healing than the low-dose group, with healing effects comparable to the positive control group. Therefore, nanofiber hydrogels loaded with 4′-hydroxychalcone can significantly promote the healing of chronic diabetic wounds, demonstrating excellent wound healing-promoting effects.

[0042] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method for preparing a 4'-hydroxychalcone-loaded nanofibrous hydrogel, characterized by, The method comprises the following steps: Step 1, mixing 4'-hydroxychalcone and polylactic acid at a mass ratio of 1: (6-12) to prepare nanofibers containing 4'-hydroxychalcone by electrospinning technology; Step 2, homogenizing the nanofibers to form short fibers; Step 3, uniformly mixing the short fibers into a hydrogel matrix composed of polyvinyl alcohol and high molecular weight hyaluronic acid; Step 4, freeze-thaw cycle treatment of the mixed hydrogel to obtain the nanofiber hydrogel carrying 4'-hydroxychalcone.

2. The method for preparing nanofiber hydrogels loaded with 4'-hydroxychalcone according to claim 1, characterized in that, In step 3, the mass ratio of polyvinyl alcohol to high molecular weight hyaluronic acid in the hydrogel matrix is (6-10):

1.

3. The method for preparing nanofiber hydrogels loaded with 4'-hydroxychalcone according to claim 1, characterized in that, In step 4, the freeze-thaw cycle treatment comprises freezing at -20℃ for 20-24 hours and then thawing at 25℃ for 1-4 hours.

4. Nanofibrous hydrogel loaded with 4'-hydroxychalcone, characterized in that, Prepared by the method of any one of claims 1-3.

5. Use of the nanofiber hydrogel carrying 4'-hydroxychalcone in claim 4 in promoting the healing of chronic wounds in diabetes.

Images