Polymer hydrogel for treating skin lesion of psoriasis and preparation method thereof

Abstract

The invention discloses drug-loaded polymer hydrogel as well as a preparation method and application thereof, and belongs to the technical field of biomedical materials. The hydrogel dressing can be used for treating mild and moderate psoriasis and improving the skin barrier function. According to the preparation method, methacrylate gelatin and carboxymethyl chitosan are taken as a hydrogel matrix, gamma-aminobutyric acid and borneol are wrapped, and sodium alginate is oxidized by a cross-linking agent, so that the cross-linking degree of the hydrogel is increased. The hydrogel disclosed by the invention can be directly injected to the skin surface and is mainly used for repairing inflammatory skin diseases such as psoriasis and wound surfaces.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, specifically to hydrogel materials, and more specifically to a polymeric hydrogel for the treatment of psoriasis lesions and its preparation method. Background Technology

[0002] Psoriasis is a common chronic, relapsing inflammatory skin disease, clinically manifested as well-defined red plaques covered with silvery-white scales, often distributed in high-tension areas such as the elbows, knees, and scalp. Histologically, it is characterized by excessive proliferation of keratinocytes, inflammatory cell infiltration, and vasodilation in the papillary dermis. Its pathogenesis involves multiple factors, including immune cell activation and overexpression of inflammatory factors (such as IL-17, IL-23, and TNF-α), forming a vicious cycle of abnormal keratinocyte proliferation and chronic inflammatory response.

[0003] Currently, clinical treatments for psoriasis include topical therapy, phototherapy, systemic drugs, and biologics. Topical medications such as corticosteroids and vitamin D derivatives can improve skin lesions in the short term, but their efficacy is limited and relapses are common. Phototherapy has some immunosuppressive effects but carries risks of carcinogenesis and phototoxicity. Systemic drugs such as methotrexate and cyclosporine are effective, but have significant toxic side effects. Biologics such as anti-IL-17 / 23 monoclonal antibodies have good efficacy, but are expensive and difficult to widely implement. Therefore, developing a safe, effective, cost-effective, and long-term applicable novel treatment strategy is of significant clinical importance.

[0004] Previous studies have shown that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) possesses multiple biological functions, including anti-inflammatory, antioxidant, and immunomodulatory effects, and can improve psoriasis symptoms by regulating immune pathways. Hydrogels, as novel drug delivery systems, exhibit good biocompatibility, sustained-release properties, and injectability, making them suitable for continuous local drug administration to psoriatic lesions. Therefore, utilizing GABA-loaded polymeric hydrogels offers a new approach to psoriasis treatment. Summary of the Invention

[0005] This invention provides a polymeric hydrogel for psoriatic lesions, along with its preparation and application, using hydrogel as a drug delivery carrier to achieve local delivery of GABA to psoriatic lesions. This hydrogel dressing can treat mild to moderate psoriasis and improve skin barrier function.

[0006] To achieve the above objectives, the design concept of this invention is as follows.

[0007] First, amino-rich natural polymers are selected as the hydrogel framework. These free amino-containing natural polymers can be collagen, gelatin, chitosan, carboxymethyl chitosan (CMCS), N-trimethyl chitosan, chitosan hydrochloride, hyaluronic acid, or amino-modified hyaluronic acid. Because gelatin has excellent biocompatibility, a simple structure, and contains a large number of free amino groups, this invention further selects gelatin to react with methacrylic anhydride to obtain methacrylate gelatin (Gel-MA). Subsequently, sodium alginate (OSA), rich in aldehyde groups, is prepared as a crosslinking agent. Then, a solution of Gel-MA, carboxymethyl chitosan (CMCS), γ-aminobutyric acid (GABA), borneol (BO), and OSA is mixed. The aldehyde groups on OSA react with the amino groups on Gel-MA and CMCS to undergo a Schiff base reaction, yielding an injectable hydrogel (GCGB-OSA).

[0008] Based on the above-described inventive concept, the injectable hydrogel provided by this invention uses methacrylate gelatin and carboxymethyl chitosan as a matrix, encapsulates γ-aminobutyric acid and borneol, and increases the cross-linking degree of the hydrogel by oxidizing sodium alginate with a cross-linking agent. The prepared hydrogel can be directly injected into psoriatic lesions or prepared into patches, microneedles, etc., for the treatment of psoriasis and other inflammatory skin diseases or skin wounds.

[0009] The preparation method of the above-mentioned hydrogel, specifically the preparation steps of Gel-MA, are as follows: gelatin is dissolved in PBS buffer, methacrylic anhydride is added dropwise, and the two react. After the reaction is complete, Gel-MA is obtained by dialysis and freeze-drying. In the reaction system, the concentration of the gelatin-PBS solution is 0.05-0.5 g / mL, the ratio of gelatin to methacrylic anhydride is 0.1-1 mL / g, preferably the concentration of the gelatin-PBS solution is 0.05-0.1 g / mL, and the reaction conditions are a 50°C water bath, pH = 7.4, and a reaction time of 2-4 hours.

[0010] The preparation method of the above hydrogel, wherein the preparation steps of OSA are as follows: sodium alginate is weighed and dissolved in deionized water (pH=5), sodium periodate solution is added, and after reacting for several hours under light-protected conditions, ethylene glycol is added to terminate the reaction, followed by dialyzing and freeze drying to obtain aldehyde-rich oxidized sodium alginate.

[0011] The above-mentioned method for preparing hydrogels includes the following mixing and crosslinking step: preparing Gel-MA solution, CMCS solution, GABA solution, BO solution, and OSA solution respectively, and mixing them evenly in proportion. The aldehyde groups on OSA react with the amino groups on Gel-MA and CMCS to form a Schiff base reaction, forming a stable three-dimensional crosslinked structure, ultimately yielding an injectable hydrogel.

[0012] The preferred range of hydrogel components is as follows: Gel-MA: 5-20% (m / v); CMCS: 5-20% (m / v); GABA: 0.01-0.2 g / mL; BO: 0.001-0.05 g / mL; OSA: 5-20% (m / v); and the solvent is an aqueous solution with a pH of 5.5-8.

[0013] In this reaction system, OSA acts as a crosslinking agent to react with Gel-MA and CMCS to form a stable three-dimensional crosslinked network, thereby obtaining a hydrogel with excellent mechanical properties and sustained-release properties.

[0014] The injectable hydrogel described in this invention can be directly injected into psoriatic lesions, completely covering the skin scales, thereby improving drug delivery efficiency; it can also be prepared into a hydrogel patch with a thickness of 1-5 mm and applied to the surface of the lesion; it can also be further prepared into a hydrogel microneedle to achieve precise transdermal delivery.

[0015] Compared with other treatments for psoriasis, this invention has the following significant advantages: ① This invention is the first to utilize sodium alginate oxide as a cross-linking agent to construct a hydrogel, with a mild preparation process, widely available raw materials, and high safety; ② Combining the inhibitory neurotransmitter GABA with the hydrogel enables local sustained-release drug delivery, effectively relieving inflammation and inhibiting excessive proliferation of keratinocytes; ③ Introducing borneol (BO) into the hydrogel can improve the transdermal absorption of GABA and simultaneously relieve patients' itching symptoms; ④ The hydrogel of this invention is an injectable system, easy to operate, and can quickly cover skin lesions, significantly improving patient compliance; ⑤ The materials are low-cost and widely available, showing good prospects for industrialization. Detailed Implementation

[0016] The technical solution of the present invention will be further described below with reference to the embodiments. The test materials used in the embodiments can all be obtained through conventional means.

[0017] Example 1

[0018] Preparation of Gel-MA: Weigh 4g of gelatin and dissolve it in 40mL of PBS buffer (pH=7.4). Add 2mL of methacrylic anhydride at 50℃ and react for 2 hours. After dialyzing (deionized water, 72 hours) and freeze drying, Gel-MA powder is obtained.

[0019] Example 2

[0020] Preparation of oxidized sodium alginate (OSA): 1.0 g of sodium alginate was dissolved in 50 mL of deionized water (pH = 5), and 1.5 g of sodium periodate (dissolved in 30 mL of deionized water) was added. The mixture was stirred in the dark for 5 hours, and the reaction was terminated by adding 2 mL of ethylene glycol and 2 g of NaCl. After dialyzing for 4 days, OSA powder was obtained by freeze-drying.

[0021] Example 3

[0022] Preparation of injectable hydrogel: Prepare 20wt% Gel-MA solution, 20wt% CMCS solution, 0.1g / mL GABA solution, 0.0375g / mL BO solution and 15wt% OSA solution, mix them in a volume ratio of 1:2:2:1:1, and let stand for several minutes to form a stable injectable hydrogel.

[0023] Example 4

[0024] Application method: Inject the hydrogel prepared in Example 3 into the psoriasis lesion, cover the scales, and let it stand for two minutes to form a dense and adherent hydrogel layer, which can play a role in local sustained-release drug delivery.

[0025] Example 5

[0026] Hydrogel patches: The above hydrogel solution is injected into a mold to form a shape, and after freeze-drying, a hydrogel patch with a thickness of about 1-5 mm is obtained, which can be directly applied to the skin lesion.

Claims

1. A method for preparing a multifunctional hydrogel dressing for treating psoriatic lesions, characterized in that, Includes the following steps: Step 1: Dissolve sodium alginate and sodium periodate in deionized water, react in the dark for 5 hours, add ethylene glycol, and continue the reaction in the dark. Step 2: Add anhydrous ethanol and sodium chloride to precipitate, dissolve the precipitate with deionized water, dialyze, and freeze dry to obtain sodium alginate oxide; Step 3: Dissolve gelatin in PBS solution, add methacrylic anhydride and stir, dialyze, freeze dry to obtain Gel-MA; Step 4: Mix Gel-MA, carboxymethyl chitosan (CMCS), γ-aminobutyric acid (GABA), borneol, and sodium alginate to prepare an injectable hydrogel.

2. The hydrogel according to claims 1-2, characterized in that, Crosslinking polymerization is achieved through a crosslinking agent. The crosslinking agent is a polymer that can induce a Schiff base reaction and form a stable three-dimensional crosslinked structure, including but not limited to sodium alginate oxide.

3. The hydrogel dressing for treating psoriatic lesions according to claims 1-3, characterized in that, It can be used to prepare topical preparations for treating psoriasis, other inflammatory skin diseases, or skin wounds, exerting a comprehensive effect of anti-inflammation, immunomodulation, promoting skin barrier repair, and antibacterial and antioxidant properties.

4. The injectable hydrogel according to claims 1-3, characterized in that, After preparation, it can be freeze-dried and stored for a long time. When used, it can be applied directly to the skin surface in the form of aerogel, or it can be used in the form of hydrogel after swelling with water. It can also be prepared into hydrogel microneedles for use.