ZNSE / POLYMER NANOCOMPOSITE-BASED TOPICAL CREAM FOR THE PREVENTION OF RADIOTHERAPY-INDUCED SKIN DAMAGE.

Abstract

This invention relates to the preparation and use of nanocomposite-based topical cream formulations developed by stabilizing ZnSe nanoparticles in a PVA / Sodium Alginate polymer matrix, for the prevention or alleviation of skin damage (such as radiodermatitis, erythema, edema, desquamation, and fibrosis) occurring during radiotherapy applications in the pharmaceutical and dermocosmetic industries.

Description

PREVENTION OF RADIOTHERAPY-INDUCED SKIN DAMAGE ZNSE / POLYMER NANOCOMPOSITE BASED TOPICAL CREAM Technical Area This invention has implications for the pharmaceutical and dermocosmetic industries, as well as for radiotherapy. skin damage that occurs during applications (radiodermatitis, erythema, for the prevention or alleviation of conditions such as edema, desquamation and fibrosis, ZnSe nanoparticles stabilized in a PVA / Sodium Alginate polymer matrix. nanocomposite-based topical cream formulations developed by It relates to its preparation and use. State of the Art In the current state of the technique, reducing skin damage after radiotherapy. For this purpose, barrier creams, steroid and moisturizer bases, usually containing ZnO, are used. The products are used with alginate or hydrogel-based topical coatings. ZnO Barrier creams containing physical barrier agents aim to reduce the incidence of radiodermatitis. It provides protection. Steroid and moisturizer-based products reduce inflammation. to suppress dryness, relieve skin irritation, and provide surface protection. Alginate and hydrogel-based coatings are used due to their moisture-retaining properties. It creates a barrier effect. However, existing products contain micron-sized ZnO. mammography and radiological artifact problem caused by particles In diagnostic imaging methods such as CT scans, radiopaque false foci (pseudo- (produces calcification), which leads to false positive diagnoses and unnecessary biopsies. can open. Also, these products have a lack of biochemical activity. It only serves as a physical barrier, preventing inflammation, oxidative stress, and tissue damage. It cannot directly influence processes such as regeneration. Furthermore, ZnO The particles cause oxidative stress and disordered Zn²⁺ release in biological environments. It can trigger inflammation, which can lead to unwanted side effects. Furthermore, institutions such as MHRA conduct pre-X-ray examinations of products containing ZnO. It has restricted its use. Description of the Invention This statement includes all those that meet the requirements mentioned above. radiotherapy that eliminates disadvantages and brings some additional advantages 2 ZnSe / Polymer nanocomposite based on the prevention of skin damage caused by various factors. The topical cream is described as having no limiting effects. The present invention satisfies the aforementioned requirements and eliminates all disadvantages. radiotherapy-induced skin lesions that eliminate and offer some additional advantages. ZnSe / Polymer nanocomposite-based topical cream for preventing damage. It is related. The primary purpose of the invention is to treat skin lesions that occur during radiotherapy treatments. damages (such as radiodermatitis, erythema, edema, desquamation and fibrosis) prevention or mitigation. Another purpose of the invention is to improve diagnostic imaging techniques such as mammography and computed tomography. artifacts that cause pseudo-opaque areas (pseudo-calcification) in the methods The goal is to reduce its formation. Another objective of the invention is to integrate ZnSe nanoparticles with PVA / Sodium Alginate polymers. By stabilizing it within the matrix, it provides both physical radiation protection and A dual-action topical formulation providing biochemical antioxidant protection. It is the development of. The invention aims to prevent and reduce skin damage caused by radiotherapy. ZnSe nanoparticles stabilized in a PVA / Sodium Alginate polymer matrix. It is a nanocomposite-based topical cream developed through this process. The invention, as preferred, consists of ZnSe nanoparticles in a PVA / Sodium Alginate polymer. homogeneous distribution within the system, thus not creating artifacts, with a biocompatible and radioprotective topical nanocomposite formulation prepared loans. The invention, in its most preferred form, is a PVA / Sodium Alginate containing ZnSe nanoparticles. a nanocomposite-based topical cream formulation for radiotherapy-induced skin It is a cream used to reduce damage. 3 The elements of the invention and their contributions to the operation are as follows. 1. ZnSe nanoparticles (1.0%): Skin particles formed during radiotherapy. Antioxidant that prevents damage and reduces radiological artifact formation. by increasing enzyme activation, it suppresses oxidative stress and affects tissue. It is an active inorganic component that accelerates regeneration. 2. Polyvinyl alcohol (PVA) (10.0%): High film-forming ability and hydroxyl thanks to the strong hydrogen bonds provided by the groups, the polymer matrix film formation that increases mechanical strength and structural stability It is a synthetic polymer that provides... 3. Sodium alginate (10.0%): With its hydrophilic structure and high water retention capacity. a gel-forming and flexible matrix together with PVA It is a natural polymer that increases homogeneity and biocompatibility. 4. Diphenhydramine HCl (1.0%): Reduces inflammation on the skin surface. It is an auxiliary component that provides and prevents irritation. 5. Camphor (0.5%): Provides a local cooling and analgesic effect on the skin surface. It is a helpful component that provides relief. 6. Glycerin (3.0%): Provides moisture-retaining properties, creating a barrier on the skin's surface. It is an auxiliary component that supports its effect and provides elasticity. 7. Stearate-11 (2.0%): Used as an emulsion stabilizer in cream formulations. It is a surfactant that maintains its homogeneity and structural integrity. 8. Ethanol (3.0%): Used as a solvent to homogenize the active and auxiliary components. It is the auxiliary phase that provides the mixture. 9. Lavender essential oil (0.2%): Provides antimicrobial and soothing properties. It is an auxiliary component that improves the dermal compatibility of the formulation. 10. Methyl paraben (0.1%); Prevents microbial contamination. It is a preservative that extends the shelf life of the formulation. 11. Deionized water (69.2%): In which all other components are dissolved and the system... It is the main solvent that ensures homogeneity. The procedural steps followed to achieve the invention are as follows: i. Nanosizing and reprocessing of ZnSe nanoparticles crystallization, ii. Preparation of PVA / Sodium Alginate polymer blend (blend film), iii. Preparation of ZnSe-doped PVA / Sodium Alginate composite films, 4 iv. Physical, chemical and radiological characterization of composite structures. carrying out the studies, v. Measurement and optimization of radiation absorption parameters. to be done, vi. Measurement and optimization of scattering (albedo) parameters. to be carried out, vii. Testing topical ZnSe application with phantom experiments, viii. Steps for performing cell culture and biochemical analyses includes. The steps involved in the production of the invention are as follows: I. Production of ZnSe Nanoparticles; ➢ Commercial ZnSe powders are heated to 70–90 °C for moisture removal. at temperature, in a vacuum environment under mbar pressure for 1–3 hours. It is dried. ➢ The dried powder is placed in a planetary ball bearing system equipped with zirconia (ZrO₂) balls. in the mill, with a ball-to-dust ratio of 10:1, at 300–500 rpm. It is ground to nanoscale size at high speed for 4–8 hours. ➢ The resulting ground ZnSe powder is mixed with N,N-dimethylformamide (DMF) and Suspended in an ethanol mixture (1:1, v / v) at a concentration of 10 mg / mL. It is done. ➢ The suspension is treated in an ultrasonic bath for 30 minutes and then ice was heated for 10 minutes with a probe sonicator at 30% amplitude. It undergoes ultrasonic processing in a bath environment. ➢ The prepared dispersion is heated in a Teflon-lined autoclave at 150–170 °C. solvothermal at temperature, for 3–6 hours and under 5–8 bar pressure It is then subjected to a recrystallization process. ➢ The ZnSe nanoparticles obtained at the end of the process are spun at 10,000 rpm. It is centrifuged for 1 minute, washed three times with ethanol, and stored at 50 °C in mbar. It is purified by drying under vacuum for 6 hours. II. Preparation of PVA / Sodium Alginate Polymer Blend Film; ➢ Polyvinyl alcohol (PVA) is mixed with pure water in a magnetic stirrer for 60–90 minutes. Mix thoroughly for 1–4 hours within the °C temperature range. It is dissolved. ➢ In a separate container, 0.250 g of Sodium Alginate (NaAlg) was purified under the same conditions. It is stirred until it dissolves in water. ➢ After both solutions have completely dissolved, the mixtures Combined and homogenized on a magnetic stirrer for approximately 4 hours. The mixing process is continued until the desired mixture is obtained. ➢ Removal of bubbles, if deemed necessary. An ultrasonic bath is applied for 5–15 minutes. ➢ The resulting homogeneous mixture is poured into clean glass petri dishes and In a vacuum oven at 35–50 °C for 18–30 hours. It is dried. ➢ After the drying process is complete, it will be homogeneous, transparent, and in one piece. PVA / Sodium Alginate mixed films are obtained in this form. III. Preparation of ZnSe-Doped PVA / Sodium Alginate Composite Films; ➢ A specified amount (1–30% by weight) of ZnSe nanoparticles, 5 30–90 minutes in an ultrasonic homogenizer in mL of chloroform. It is dispersed over a period of time. ➢ After achieving a completely homogeneous distribution, the ZnSe dispersion, It is slowly added to the prepared PVA / Sodium Alginate mixture. ➢ The mixture is stirred in a magnetic stirrer for 2 hours to activate ZnSe. homogeneous distribution of nanoparticles within a polymer matrix It is provided. ➢ The resulting ZnSe-doped mixture is poured into glass petri dishes and It is dried in a vacuum oven at a temperature of 35–50 °C for 18–30 hours. ➢ After the drying process is complete, it will be transparent, homogeneous and Integrated ZnSe / PVA / Sodium Alginate nanocomposite films were obtained. It is done. IV. Characterization Studies; ➢ Chemical, morphological and structural characteristics of the resulting nanocomposite films Analyses include FTIR, XPS, TEM, XRD, TGA / DSC, Raman, Zeta. This is performed using potential and UV-Vis devices. ➢ Radiation absorption parameters (MAC, HVL, MFP, etc.) 17–242 It is measured in the keV energy range. ➢ Scattering (albedo) parameters are in the energy range of 23–225 keV and It is determined between scattering angles of 120°–180°. 6 V. Clinical Phantom Tests; ➢ The prepared ZnSe / PVA / Sodium Alginate nanocomposite films are used on tissue. Its equivalent is placed inside the phantom. ➢ Subjected to irradiation by a linear accelerator (LINAC) with photon energy of 6–18 mV. It is held. ➢ SSD (source-to-surface distance) should be 95–105 cm, 8x8 – 12×12 cm² area dimensions, 180–220 Monitor Units (MU) and The test is performed with an irradiation time of 100–300 seconds. ➢ The dosage range is determined between 100–600 cGy. ➢ Effect of film layers on dose distribution within the phantom ion chamber It is evaluated through measurements. VI. Cell Culture and Biochemical Analyses; ➢ Human keratinocyte (HaCaT) and mouse fibroblast (L929) cell lines in vitro cytotoxicity, live / dead cell analysis, wound Recovery is assessed by analyzing ROS, MDA, SOD, CAT, and GPx activities. ➢ Cells are maintained at a temperature of 36–38 °C, 4–6% CO₂ and 90–95% humidity. It is incubated under these conditions. ➢ Culture media for HaCaT were DMEM (8–12% FBS, 0.5–1.5%) respectively. L929 contains MEM (8–12% serum, antibiotic), antibiotic. ➢ Cell viability detected by XTT test (in the 450–500 nm absorbance range) Evaluation is performed after 12–72 hours of incubation. ➢ Live / dead cell analysis with Annexin V-FITC / PI staining 24–48 hours It is done after exposure. ➢ Cellular uptake via confocal microscopy or XRF method in 6–48 hours It is observed between them. ➢ Wound healing test is initiated at 80–90% cell density and 0–48 It is monitored periodically between certain hours. ➢ Oxidative stress and antioxidant parameters in the 15–72 hour range It is analyzed using ROS, MDA, SOD, CAT, and GPx tests. Method of Implementing the Invention; a) ZnSe / PVA / Sodium Alginate nanocomposite developed within the scope of the invention a topical cream based on radiotherapy, applied locally to skin areas exposed to radiotherapy. It is implemented as follows. 7 b) Before application, the skin surface is cleaned and the formulation is applied in a thin layer. It is then driven into the target area. c) The applied cream is formed by polymer phases of PVA and Sodium Alginate. The film creates a physical barrier layer on the skin. d) ZnSe nanoparticles accumulate locally on the skin surface, absorbing radiation. reduces its effect and in diagnostic imaging procedures such as mammography and CT scans. It prevents artifact formation. e) Antioxidant enzymes as a result of the biochemical effects of Zn and Se elements Oxidative stress is suppressed by increasing the activities of sodium oxidases (SOD, CAT, GPx). f) As a result of the application, both a physical radiation barrier and Biochemical protection is provided; skin healing process after radiotherapy. It is accelerated. Other Features of the Invention; ✓ The invention enables mammography thanks to the homogeneous distribution of ZnSe nanoparticles. Pseudocalcification in imaging methods such as CT and digital X-rays. It prevents the formation of (pseudo-calcification). ✓ PVA / Sodium Alginate dual phase polymer system, ZnSe nanoparticles It ensures controlled release and a long-lasting protective effect. ✓ The invention offers both physical radiation protection and biochemical antioxidant properties. It offers a dual-action structure by providing protection. ✓ The production method is low-cost and involves solution casting and hydrogel formulation. And it is suitable for industrial application with techniques such as electrospinning. ✓ It can be commercialized in the pharmaceutical, dermocosmetic, and medical device sectors; Also, radiology personnel, nuclear medicine applications, phototherapy, dentistry. as a local radioprotective barrier in fields such as medicine and veterinary medicine available.

Claims

1. The invention relates to radiotherapy in the pharmaceutical and dermocosmetic industries. skin damage that occurs during applications (radiodermatitis, erythema, to prevent or alleviate (such as edema, desquamation and fibrosis) It is a nanocomposite-based topical cream formulation used, and its characteristic feature is; Biochemical antioxidant protection that reduces radiological artifact formation. a polymer of polyvinyl alcohol (PVA) and sodium alginate (NaAlg) Nano-sized zinc selenide homogeneously distributed within the matrix. It contains (ZnSe) nanoparticles.

2. Compliant with Claim 1, its characteristic feature is that the weight-based preferred component ratios are: ZnSe nanoparticles 1.0%; Polyvinyl alcohol (PVA) 10.0%; Sodium Alginate 10.0%; Diphenhydramine HCl 1.0%; Camphor 0.5%; Glycerin 3.0%; Stearate-11 2.0%; Ethanol 3.0%; Lavender essence 0.2%; Methyl paraben 0.1%; Distilled water It contains 69.2%.

3. Complies with Claim 1, its characteristic is; ZnSe nanoparticles in PVA and Sodium The alginate is homogeneously dispersed within the polymer phase, thus allowing for controlled release. and it includes a system that provides long-term protection.

4. Complies with Claim 1, and its characteristic is; diagnostic procedures such as mammography and computed tomography. pseudo-calcification that does not create artifacts in imaging methods It should be a structure that does not create (false opaque areas).

5. Complies with Claim 1, and its characteristic is; PVA / Sodium Alginate after application. the polymer phase forms a transparent, elastic film layer on the skin, and this in a structure where the layer enables the controlled release of ZnSe nanoparticles It is the fact that.

6. Complies with Claim 1, its characteristic is that the elements Zn and Se act as antioxidant enzymes. by increasing their activities (SOD, CAT, GPx) they suppress oxidative stress and damage tissue It exhibits a biochemical protective effect that accelerates regeneration. 9 7. Complies with Claim 1, and its characteristics are: Diphenhydramine HCl, Camphor and Lavender essence. Thanks to its components, it has anti-inflammatory, cooling and antimicrobial effects. It contains auxiliary phases which indicates that it contains auxiliary phases.

8. Complies with Claim 1, and its characteristic is; to skin areas exposed to radiotherapy. By being applied locally, it both reduces the negative effects of radiation and... It is a cream that does not create diagnostic imaging artifacts.