Gel for preventing radiodermatitis

Abstract

The invention discloses a gel for preventing radiodermatitis. According to the invention, firstly, iNOS-DNA enzyme is designed, and the nucleotide sequence of the iNOS-DNA enzyme is shown as SEQ ID NO.1; the preparation method comprises the following steps: dissolving iNOS-DNA enzyme and cobalt nitrate in methanol to obtain a solution A, and dissolving dimethylimidazole in methanol to obtain a solution B; the solution A and the solution B are mixed and stirred, and iNOS-DZ-ZIF-67 is obtained; the preparation method comprises the following steps: dissolving hyaluronic acid in a sodium acetate solution to obtain a hyaluronic acid (HA) solution, adding iNOS-DZ-ZIF-67 / HA into the hyaluronic acid (HA) solution, stirring in a dark place, freeze-drying and precipitating, and adding water and mixing when in use to obtain the gel for preventing radiodermatitis. The prepared gel has good stability, slow release property and angiogenesis effect, the delivery rate and antibacterial property can be improved, and radiodermatitis can be prevented and treated in a targeted mode.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, specifically to a gel for preventing radiation dermatitis. Background Technology

[0002] Radiation dermatitis (RD) is an acute or chronic injury to the skin caused by various types of ionizing radiation, including alpha, beta, gamma, and X-rays. The incidence of RD in radiotherapy patients is over 90%, and it can also occur in occupational radiation exposure, radiation accidents, and nuclear war. Therefore, how to prevent RD has become a pressing and challenging issue in the field of radiation protection. In recent years, biomaterials with safety, effectiveness, and cost-effectiveness have become a new focus in RD prevention. In the development of radiation dermatitis, inducible nitric oxide synthase (iNOS) plays a central pathological driving role. The mechanism involves ionizing radiation directly damaging skin cell DNA and triggering oxidative stress, while simultaneously activating signaling pathways, including NF-κB, inducing high expression of iNOS in epidermal keratinocytes and infiltrating immune cells. Therefore, excessive activation of iNOS permeates the entire process of radiation dermatitis, from initial damage and inflammation amplification to delayed repair, becoming a core molecular bridge connecting physical radiation damage and complex biological lesions. However, there are currently few reports on the use of iNOS to treat inflammation.

[0003] DNAzymes (DZs) are single-stranded DNA sequences with catalytic activity obtained through in vitro design and screening. They can cleave RNA-based viruses or act as gene silencing molecules in diseases involving elevated levels of non-coding RNA or certain proteins. However, research on iNOS-DNAzymes is currently lacking. DNAzymes (DZs) can target and cleave specific mRNAs. For example, patent application CN 118340716 A discloses a miR155 / iNOS-DZ@CuTz-1 biogel, its preparation method, and its applications. iNOS-DZ can degrade iNOS and simultaneously link the signal miR155. CuTz-1 is a monodisperse copper-based metal-organic framework material that can load oxygen to alleviate local skin hypoxia, while also clearing overexpressed glutathione, reducing oxidative stress, and can also be used to encapsulate miR155 / iNOS-DZ. The prepared miR155 / iNOS-DZ@CuTz-1 biogel can effectively promote wound healing in mice with radiation dermatitis. miR-155 is a typical inflammation-associated miRNA, upregulated by many inflammations, infections, immune activation, and tissue damage. Therefore, when miR-155 is used as a "specific early signal for radiation dermatitis," it may be triggered even in non-radiation-induced skin inflammations (such as infections, friction irritation, and allergic dermatitis), leading to premature / excessive release of the material. However, iNOS-DNAase alone is easily inactivated, difficult to deliver, and has a limited function. Therefore, how to utilize iNOS-DNAase to treat radiation dermatitis while improving delivery rate and antibacterial activity, thereby enhancing the therapeutic effect, is a problem that needs to be solved. Summary of the Invention

[0004] To address the aforementioned limitations of existing technologies, the present invention aims to provide a gel for preventing radiation dermatitis. The present invention designs an iNOS-DNA enzyme, encapsulates it in ZIF-67, and externally attaches hyaluronic acid to the ZIF-67 to obtain a gel for preventing radiation dermatitis. This gel exhibits good stability, sustained-release properties, and angiogenesis activity, and can improve delivery rate and antibacterial activity, enabling targeted prevention and treatment of radiation dermatitis.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: In a first aspect, the present invention provides a gel for preventing radiation dermatitis, prepared by the following method: (1) iNOS-DNAase and cobalt nitrate were dissolved in methanol to obtain solution A, and dimethyl imidazole was dissolved in methanol to obtain solution B; solution A and solution B were mixed and stirred, centrifuged and washed to obtain precipitate, and the precipitate was freeze-dried to obtain iNOS-DZ@ZIF-67; (2) Hyaluronic acid is dissolved in sodium acetate solution to obtain hyaluronic acid solution, iNOS-DZ@ZIF-67 is added, stirred in the dark, centrifuged and washed to obtain precipitate, and the precipitate is freeze-dried to obtain iNOS-DZ@ZIF-67 / HA. iNOS-DZ@ZIF-67 / HA is dissolved in water to obtain gel for preventing radiation dermatitis.

[0006] Preferably, in step (1), the nucleotide sequence of the iNOS-DNA enzyme is as shown in SEQ ID NO.1: GGCAAGCCAGGCTAGCTACAACGAGTCTGAGAC.

[0007] Preferably, in step (1), the ratio of cobalt nitrate, iNOS-DNA enzyme and methanol added is (0.7~0.8) g: 0.25 mg: 50 mL; the concentration of dimethicone in solution B is 0.03~0.035 g / mL.

[0008] Preferably, in step (1), the volume ratio of solution A to solution B is 1:1; and the stirring time is 8 hours.

[0009] Preferably, in step (1), the washing is performed by washing with methanol three times; the freeze-drying temperature is -20°C and the freeze-drying time is 2 hours.

[0010] Preferably, in step (2), the concentration of the sodium acetate solution is 0.2M; the concentration of the hyaluronic acid solution is 2mg / mL; and the ratio of the amount of iNOS-DZ@ZIF-67 added to the amount of hyaluronic acid solution is 10mg:10mL.

[0011] Preferably, in step (2), the stirring time in the dark is 24 hours.

[0012] Preferably, in step (2), the washing is performed by washing with methanol three times; the freeze-drying temperature is -20°C and the freeze-drying time is 2 hours.

[0013] Preferably, in step (2), iNOS-DZ@ZIF-67 / HA and water are mixed at a ratio of 1 mg: 1 mL, and iNOS-DZ@ZIF-67 / HA is dissolved in water to form a gel for preventing radiation dermatitis.

[0014] A second aspect of the invention provides the use of the above-described gel in improving the delivery rate of iNOS-DZ or in the preparation of products for treating radiation dermatitis.

[0015] The beneficial effects of this invention are: (1) This invention designs an iNOS-DNAase. iNOS-DZ and ZIF-67 are synthesized as an intermediate product iNOS-DZ@ZIF-67 using a one-pot method and self-assembly embedding. HA is then chemically bonded to the surface of iNOS-DZ@ZIF-67 to synthesize iNOS-DZ@ZIF-67 / HA. This gel has good stability, sustained release, and angiogenesis effects, and can improve delivery rate and antibacterial properties, enabling targeted prevention and treatment of radiation dermatitis.

[0016] (2) The gel preparation method of the present invention is simple, and the prepared gel effectively solves the problems of easy inactivation and difficult delivery of iNOS-DNAase. It is convenient to use and can effectively treat and prevent radiation dermatitis. The iNOS-DZ in the present invention has targeting properties, which only cleaves iNOS mRNA, thereby inhibiting iNOS expression, ultimately inhibiting the inflammatory pathway, promoting HaCaT cell migration, angiogenesis and anti-apoptosis, thereby preventing and treating radiation dermatitis. The hydrophobicity of iNOS-DZ@ZIF-67 / HA can inhibit the adhesion / diffusion of exogenous bacteria and other microorganisms on the one hand, and can play a sustained-release role when used to treat radiation dermatitis on the other hand. Attached Figure Description

[0017] Figure 1 Design the iNOS-DZ sequence; (a) thermodynamic parameters of iNOS-DZ; (b) sequence structural features of iNOS-DZ; (c) secondary structure of iNOS-DZ; (d) simulation diagram of iNOS-DZ binding process with substrate chain. Figure 2 Morphological characteristics and physicochemical properties analysis of iNOS-DZ@ZIF-67 / HA: (a) Scanning electron microscopy (SEM) image of the material; (b) Particle size of the material; (c) Zeta charge of the material; (d) Transmission electron microscopy (TEM) image of the material; (e) X-ray diffraction pattern (XRD) of the material; (f) Fourier transform infrared spectroscopy (FT-IR) image of the material; (g) Atomic force microscopy (AFM) image of the material; (h) Elemental analysis spectrum (EDS) of the material; (i) X-ray photoelectron spectroscopy (XPS) image of the material; (j) Contact angle image of the material; Figure 3In vitro cellular functions of iNOS-DZ@ZIF-67 / HA; (a) Analysis of the effect of AE treatment on cell morphology; (b) Analysis of the effect of AE treatment on cell apoptosis; (c) Effect of AE treatment on cell migration; (d) Statistical analysis of the in vitro antibacterial activity of the material; (e) Analysis of the effect of AE treatment on cell proliferation; (f) Statistical analysis of the effect of AE treatment on cell apoptosis rate; (g) Statistical analysis of the effect of AE treatment on cell migration rate; (h) Statistical analysis of the survival rate of antibacterial bacteria in vitro treated with AE treatment; (i) Effect of AE treatment on cellular IFN-γ expression; (j) Effect of AE treatment on cellular iNOS expression. (This represents P < 0.05). Detailed Implementation

[0018] It should be noted that the following detailed descriptions are illustrative and intended to provide further explanation of this application. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains.

[0019] As described in the background section, research on iNOS-DNAase is currently lacking. While DNAase (DZ) can target and cleave specific mRNAs, iNOS-DNAase is easily inactivated, difficult to deliver, and has limited functionality when used alone.

[0020] Based on this, the purpose of this invention is to provide a gel containing iNOS-DNase for the prevention of radiation dermatitis. This invention first selects a specific recognition sequence based on the iNOS mRNA sequence, and designs a DNase, iNOS-DZ, that can specifically recognize and cleave iNOS. Because iNOS-DZ is easily inactivated, difficult to deliver, and has a single function, it is encapsulated in ZIF-67, and hyaluronic acid is externally attached to ZIF-67 to obtain the gel for preventing radiation dermatitis. The iNOS-DZ of this invention is targeted, cleaving only iNOS mRNA, thereby inhibiting iNOS expression, ultimately suppressing inflammatory pathways, promoting HaCaT cell migration, angiogenesis, and anti-apoptosis, thereby preventing and treating radiation dermatitis. Furthermore, the iNOS-DZ@ZIF-67 / HA prepared in this invention also exhibits hydrophobicity. Although HA has a higher yield rate due to its hydrophilicity, the overall hydrophilicity / hydrophobicity of iNOS-DZ@ZIF-67 / HA is determined by the main carrier (ZIF-67 hydrophobicity) + HA, with hydrophobicity being the dominant property (see...). Figure 2 On the one hand, it can inhibit the adhesion / diffusion of exogenous bacteria and other microorganisms; on the other hand, it can have a sustained-release effect when used to treat radiation dermatitis.

[0021] To enable those skilled in the art to better understand the technical solution of this application, the technical solution of this application will be described in detail below with reference to specific embodiments.

[0022] The test materials used in the embodiments of this invention are all conventional test materials in the art and can be purchased through commercial channels.

[0023] Example 1 (1) Based on bioinformatics and molecular dynamics simulation websites, the mRNA sequence of iNOS was retrieved, and a targeted cleavage sequence of iNOS-DZ was designed. Its nucleotide sequence is shown in SEQ ID NO.1: GGCAAGCCAGGCTAGCTACAACGAGTCTGAGAC.

[0024] (2) Screening of iNOS-DZ using bioinformatics and molecular dynamics simulations, including simulations of iNOS-DZ's thermodynamic parameters, sequence structure characteristics, and substrate chain binding process. Figure 1 a~ Figure 1 d). The displayed sequence theoretically possesses the ability to cleave iNOS mRNA.

[0025] Example 2 (1) 0.727 g cobalt nitrate and 250 μ g of iNOS-DNAase from Example 1 were dissolved in 50 ml of methanol to obtain solution A; 1.64 g of dimethicone was dissolved in 50 ml of methanol to obtain solution B. Solution A and solution B were mixed and stirred for 8 h, centrifuged, and washed three times with methanol. The resulting precipitate was freeze-dried into powder to obtain iNOS-DZ@ZIF-67.

[0026] (2) Prepare 10 mL of HA solution with a concentration of 2 mg / mL (hyaluronic acid dissolved in 10 mL of 0.2 M sodium acetate solution), add 10 mg of iNOS-DZ@ZIF-67 to the above HA solution, stir in the dark for 24 h, centrifuge, wash with methanol 3 times, freeze-dry the obtained precipitate into powder to obtain iNOS-DZ@ZIF-67 / HA.

[0027] To use, dissolve 1 mg of iNOS-DZ@ZIF-67 / HA in 1 mL of water to create a gel for preventing radiation dermatitis.

[0028] Comparative Example 1 miR155 / iNOS-DZ@CuTz-1 biogel was prepared using the iNOS-DNAase of Example 1. The preparation method was carried out according to the method of Example 2 in the application CN 118340716 A entitled "A miR155 / iNOS-DZ@CuTz-1 biogel and its preparation method and application".

[0029] (1) Preparation of miR155 / iNOS-DZ enzyme solution: Dissolve miR155-5p in deionized water to obtain a miR155 solution of 1 μg / μL; dissolve iNOS-DZ in water to obtain an iNOS-DZ solution of 1 μg / μL in deionized water; add 50 μL of the 1 μg / μL miR155 solution to 100 μL of the 2 μg / μL iNOS-DZ solution and react at 60 °C for half an hour. The two sequences self-assemble and combine to obtain the miR155 / iNOS-DZ enzyme solution.

[0030] (2) Synthesis of CuTz-1: 550 mg of 3,5-ph2-tzh (3,5-diphenyl-1,2,4-triazole) was mixed in 100 ml of methanol and 10 ml of deionized water to prepare a precursor solution. Then, 1.5 g of Cu(CH3CN)4BF4 was added. The mixture was stirred at room temperature for 3 hours, then centrifuged at 8000 rpm for 5 min. The supernatant was discarded, and the precipitate was washed three times with methanol and then freeze-dried to obtain CuTz-1.

[0031] (3) Preparation of miR155 / iNOS-DZ@CuTz-1: Weigh 250mg CuTz-1, dissolve it in 15mL PBS buffer, add 10mL miR155 / iNOS-DZ enzyme solution, stir at room temperature for 24h, freeze dry after the reaction is complete to obtain miR155 / iNOS-DZ@CuTz-1 biogel.

[0032] Example 3: Characterization (1) Figure 2 Morphological characteristics and physical properties analysis of iNOS-DZ@ZIF-67 / HA prepared in Example 2. Figure 2 The image shows the morphological characteristics and physical property analysis of the final DNA enzyme material. Figure 2 a, Figure 2 d、 Figure 2 g shows the scanning electron microscope (SEM), transmission electron microscope (TEM), and atomic force microscope (AFM) images of the material, indicating that the material has a typical core-shell multifaceted cubic structure, which is basically consistent with the morphology and structure of ZIF-67 reported in some literature. Figure 2 b shows that the final material particle size is approximately 100-300 nm, exhibiting nanomaterial characteristics; Figure 2 c indicates that the material ultimately carries a negative charge, primarily due to the negative charge of HA, which is beneficial for enhancing its antibacterial properties. These results preliminarily suggest that the DNase material possesses unique crystal morphology characteristics, as well as nanoparticle size and a negative charge. Figure 2h is the elemental analysis spectrum (EDS), which clearly shows the presence of elements such as C, N, and O, especially Co, indicating that ZIF-67 was successfully loaded. Figure 2 e, 2f, and 2i are the X-ray diffraction (XRD), Fourier transform infrared (FT-IR), and X-ray photoelectron spectroscopy (XPS) images of the material, showing the typical absorption peaks and spectral morphology unique to the material, especially the two components ZIF-67 and HA. The peak shapes are slightly shifted (Figure 2f), indicating that a chemical interaction has formed between the two (a typical feature of grafting). Figure 2 The "j" indicates that the material has a certain degree of hydrophobicity. These results preliminarily indicate that the DNase material has been successfully prepared and possesses its unique chemical properties.

[0033] (2) The iNOS-DZ release rate experiment (cumulative release rate, %) was carried out on the iNOS-DZ@ZIF-67 / HA prepared in Example 2 and the miR155 / iNOS-DZ@CuTz-1 biogel prepared in Comparative Example 1.

[0034] iNOS-DZ Release Rate: 1. Accurately weigh 5 mg of each of the two materials (3 replicates per group), dissolve them in 5 mL of PBS buffer (pH=7.4, 37℃, simulating physiological environment), and add them to the dialysis bag; 2. Place the dialysis bag in 50 mL of the same PBS buffer, and incubate at 37℃ with constant shaking at 100 rpm. At 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 h, take 5 mL of the dialysis fluid and simultaneously add 5 mL of fresh PBS (to maintain a constant system volume); 3. Determine the concentration of iNOS-DZ or Co / imidazole in the dialysis fluid using a fluorescent labeling method, and calculate the release amount of iNOS-DZ based on the standard curve. Calculation method: Cumulative release rate (%) = (Total release amount of iNOS-DZ in the dialysis fluid at each time point / Total iNOS-DZ loading in the material) × 100%.

[0035] iNOS-DZ encapsulation efficiency (%): 1. Accurately weigh 10 mg of each of the two materials and dissolve them separately in 10 mL of PBS buffer (pH=7.4). After thorough shaking and dissolution, centrifuge at 12000 r / min and 4℃ for 20 min, and collect the supernatant; 2. Quantitative quantification of the concentration of free iNOS-DZ in the supernatant is performed using fluorescence, and the mass of free iNOS-DZ is calculated according to the standard curve. Calculation method: Encapsulation efficiency (%) = (Total mass of iNOS-DZ - Mass of free iNOS-DZ in supernatant) / Total mass of iNOS-DZ × 100%.

[0036] The results are shown in Table 1.

[0037] Table 1 Release rate and encapsulation efficiency As shown in Table 1, the cumulative release rate of iNOS-DZ by iNOS-DZ@ZIF-67 / HA was significantly higher than that by miR155 / iNOS-DZ@CuTz-1 at all time points. At 72 hours, the former's cumulative release rate reached 89.3%, while the latter's was only 67.9%, indicating that iNOS-DZ@ZIF-67 / HA had a superior release effect on iNOS-DZ. The encapsulation efficiency of iNOS-DZ by iNOS-DZ@ZIF-67 / HA (89.6%) was significantly higher than that of miR155 / iNOS-DZ@CuTz-1 (75.8%), indicating that the former had a stronger encapsulation capacity for iNOS-DZ and could load more iNOS-DZ.

[0038] Test case (1) Evaluation of material biocompatibility and cell morphology: In vitro experiments were divided into 5 groups: Group A was normal cell group, Group B was normal cell + 3Gy irradiation group, Group C was normal cell + 3Gy irradiation + iNOS-DZ group, Group D was normal cell + 3Gy irradiation + iNOS-DZ@ZIF-67 group, and Group E was normal cell + 3Gy irradiation group + iNOS-DZ@ZIF-67 / HA group. The AE group was co-cultured with Hacat cells (human cell line, cryopreserved from the First Affiliated Hospital of Army Medical University) for 7 days. CCK-8 reagent was added on days 1, 3, and 5 of culture, and the absorbance value at 450nm was measured by a multi-functional microplate reader to compare the cell viability of different groups at different time points. At the same time, after treatment in the above manner, cells were stained with DAPI to observe the effect of co-culture on cell morphology.

[0039] In vitro antibacterial function of the materials: The above five treatments were co-cultured with methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) for 12 h, the precipitate was resuspended, and an appropriate dilution was spread on nutrient agar plates. After incubation at 37°C for 12 h, the plates were counted using an automatic colony counter.

[0040] Effects of materials on cell migration: The five treatments were co-cultured with Hacat cells for 24 h, and the cells were placed under a live cell workstation for 12 h using a scratch assay to determine the effects of materials on cell migration.

[0041] Effects of materials on in vitro angiogenesis: 2×10 3 HUVEC cells were seeded into 96-well plates coated with Matrigel and then added to the AE group. After 24 hours of stimulation, angiogenesis was imaged using an Olympus microscope.

[0042] The effect of materials on apoptosis: Apoptosis was measured using flow cytometry and the VFITC / PI apoptosis detection kit.

[0043] (2) HaCaT cell staining showed that iNOS-DZ@ZIF-67 / HA can effectively improve cell morphology after radiation. Figure 3 a), CCK-8 showed low cytotoxicity ( Figure 3 e), and was superior to groups C and D. Apoptosis experiments showed ( Figure 3 b and Figure 3 f), iNOS-DZ@ZIF-67 / HA effectively inhibited apoptosis (p<0.05). Migration studies showed that ( Figure 3 c and Figure 3 g), iNOS-DZ@ZIF-67 / HA can promote the migration of HaCaT cells after radiation (p<0.05). Antibacterial experiments showed that ( Figure 3 d and Figure 3 The material effectively inhibited the growth of Gram-positive bacteria (MRSA) and Gram-negative bacteria (E. coli) (p<0.05). Western blot experiments showed that the material effectively inhibited radiation-induced high expression of iNOS and IFN-γ. Figure 3 j and Figure 3 i, p<0.05). In summary, the above results all indicate that iNOS-DZ@ZIF-67 / HA has low toxicity, can promote migration and inhibit apoptosis by inhibiting the high expression of iNOS and IFN-γ, and also has good antibacterial activity.

[0044] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A gel for preventing radiation dermatitis, characterized in that, Prepared by the following method: (1) iNOS-DNAase and cobalt nitrate were dissolved in methanol to obtain solution A, and dimethyl imidazole was dissolved in methanol to obtain solution B; solution A and solution B were mixed and stirred, centrifuged and washed to obtain precipitate, and the precipitate was freeze-dried to obtain iNOS-DZ@ZIF-67; (2) Hyaluronic acid is dissolved in sodium acetate solution to obtain hyaluronic acid solution, iNOS-DZ@ZIF-67 is added, stirred in the dark, centrifuged and washed to obtain precipitate, and the precipitate is freeze-dried to obtain iNOS-DZ@ZIF-67 / HA. iNOS-DZ@ZIF-67 / HA is dissolved in water to obtain gel for preventing radiation dermatitis.

2. The gel according to claim 1, characterized in that, In step (1), the nucleotide sequence of the iNOS-DNA enzyme is shown in SEQ ID NO.

1.

3. The gel according to claim 1, characterized in that, In step (1), the ratio of cobalt nitrate, iNOS-DNA enzyme and methanol added is (0.7~0.8) g: 0.25 mg: 50 mL; the concentration of dimethicone in solution B is 0.03~0.035 g / mL.

4. The gel according to claim 1, characterized in that, In step (1), the volume ratio of solution A to solution B is 1:1; the stirring time is 8 hours.

5. The gel according to claim 1, characterized in that, In step (1), the washing is performed by washing with methanol three times; the freeze-drying temperature is -20℃ and the freeze-drying time is 2 hours.

6. The gel according to claim 1, characterized in that, In step (2), the concentration of the sodium acetate solution is 0.2M; the concentration of the hyaluronic acid solution is 2mg / mL; and the ratio of the amount of iNOS-DZ@ZIF-67 added to the amount of hyaluronic acid solution is 10mg:10mL.

7. The gel according to claim 1, characterized in that, In step (2), the stirring time in the dark is 24 hours.

8. The gel according to claim 1, characterized in that, In step (2), the washing is performed by washing with methanol three times; the freeze-drying temperature is -20℃ and the freeze-drying time is 2 hours.

9. The gel according to claim 1, characterized in that, In step (2), iNOS-DZ@ZIF-67 / HA and water are mixed at a ratio of 1 mg: 1 mL. Dissolving iNOS-DZ@ZIF-67 / HA in water yields a gel for preventing radiation dermatitis.

10. The use of the gel according to any one of claims 1 to 9 in improving the delivery rate of iNOS-DZ or in the preparation of products for treating radiation dermatitis.

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