Investigation of the efficacy of gelatin-tannin hydrogels for the delivery of biologically active substances using curcumin as an example

Wound healing is a complex process that requires a comprehensive approach to treatment. Hydrogel materials modified with bioactive substances (BAS) are currently under active development. Such materials represent an alternative to conventional dressings. The inclusion of BAS in their composition opens the way to providing the required properties (antiseptic, antioxidant, etc.). Curcumin is one of a number of polyflavonoids that are being intensively studied for such use. Objective: in the current work, the method of obtaining gelatin-tannin hydrogels with BAS (curcumin), as well as the efficiency of isolation of the injected substance in vitro and the characteristics of its binding to the polymer matrix are considered. Materials and methods. The object of the study is gelatin-tannin hydrogels with curcumin. The structure of the materials was studied by IR spectroscopy, the sorption parameters were determined gravimetrically, the release of curcumin was studied by visible spectroscopy and analyzed using conventional pharmacokinetic models. Results. In the course of the work, hydrogel materials based on gelatin and tannin with a curcumin content from 0.1 to 1.0% were synthesized. It was found that the incorporation of curcumin into the polymer mesh was successful and curcumin is not released from hydrogels when swelling in distilled water. The introduction of curcumin into the formulation reduced the sorption capacity of hydrogels in distilled water from 15 g/g to 7-9 g/g. The Higuchi model (R²>0.95) was determined to be the most optimal model describing the process of curcumin extraction from materials. Using the description of the release kinetics, it was determined that the maximum release (22%) was achieved with a minimum curcumin content in the hydrogel (0.1 wt.%) and the minimum release speed. Conclusion. A method for the synthesis of gelatin-tannin hydrogels with curcumin has been developed. The structure of materials, sorption capacity, and the ability to release BAS have been studied. Further prospects for the inclusion of other BAS of a hydrophobic nature in the composition of hydrogels are shown.

1. Nguyen M.K., Alsberg E. Bioactive factor delivery strategies from engineered polymer hydrogels for therapeutic medicine. Prog Polym Sci. 2014;39(7):1236-1265. DOI: 10.1016/j.progpolymsci.2013.12.001.

2. Morgacheva A.A., Artyukhov A.A., Panov A.V., Gordienko M.G., Shtilman M.I., Mezhuyev Ya.O. Synthesis of polyvinyl alcohol with methacrylate groups and hydrogels based on it.Russian Journal of Applied Chemistry. 2015;88(4): 617-621. DOI: 10.1134/S1070427215040102. EDN: UFABCL

3. Senokosova E.A., Rezvova M.A., Sevostyanova V.V., Matveeva V.V. The first results of creating a hybrid hydrogel based on fibrin and polyvinyl alcohol: comparison with monocomponent hydrogels. The Siberian journal of clinical and experimental medicine. 2023;38(1):140-150 (in Russ.). DOI: 10.29001/2073-8552-2023-38-1-140-150. EDN: GAHUCO.

4. Kumar S.S.D., Houreld N.N., Abrahamse H. Biopolymer-Based Composites for Medical Applications. Encyclopedia of Renewable and Sustainable Materials. Vol. 2. Elsevier Ltd.; 2020:20-28. DOI: 10.1016/B978-0-12-803581-8.10557-0.

5. Grigor’yev A.M., Basok Yu.B., Kirillova A.D., Surguchenko V.A., Shmerko N.P., Kulakova V.K., Ivanov R.V., Lozinskiy V.I., et al. Cryogenically structured gelatin-based hydrogel as a resorbable macroporous matrix for biomedical technologies.Russian journal of transplantology and artificial organs. 2022;24(2):83-93 (in Russ.). DOI: 10.15825/1995-1191-2022-2-83-93. EDN: DSIQGI.

6. Pletnev M.Y., Pokid’ko B.V., Trybala A., Starov V.M. Gelatin hydrogel as a model for assessing the wettability and water resistance of polypeptide materials. Colloidal Journal. 2015;77(3):321-326. DOI: 10.1134/S1061933X1503014X. EDN: UGBPUR.

7. Shen Y., Farajtabar A., Xu J., Wang J., Xia Y., Zhao H., Xu R. Thermodynamic solubility modeling, solvent effect and preferential solvation of curcumin in aqueous co-solvent mixtures of ethanol, n-propanol, isopropanol and propylene glycol. J Chem Thermodyn. 2019;131:410-419. DOI: 10.1016/j.jct.2018.11.022.

8. Kumari A., Raina N., Wahi A., Goh K.W., Sharma P., Nagpal R., Jain A., Ming L.C., Gupta M. Wound-Healing Effects of Curcumin and Its Nanoformulations: A Comprehensive Review. Pharmaceutics. 2022;14(11):2288. DOI: 10.3390/pharmaceutics14112288.

9. Beschastnov V.V., Yudanova T.N., Aref’yev I.Yu., Chernyshev S.N., Pogodin I.E., Pavlenko I.V., Tulupov A.A., Leont’yev A.E. Possibilities of using hydrogel compositions in the treatment of wounds. Mosc Surg J. 2019;6(70):17-22 (in Russ.). DOI: 10.17238/issn2072-3180.2019.6.17-22. EDN: VEGZSN.

10. Khisamova A.A., Gizinger O.A., Kornova N.V., Zyryanova K.S., Korkmazov A.M., Beloshangin A.S. Studies of immunological and microbiological efficiency of the therapy of curcumin and methionine in the developed capsules.Russian Journal of Immunology. 2021;24(2):305-310 (in Russ.). DOI: 10.46235/1028-7221-1001-SOI. EDN: NTFRNZ.

11. Snetkov P.P., Sitnikova V.E., Uspenskaya M.V., Morozkina S.N., Olekhnovich R.O. Hyaluronic acid - curcumin electrospun fibers.Rus Chem Bul. 2020;(3):596-600 (in Russ.). EDN: DFJRQQ.

12. Kushnir T.I., Arnotskaya N.E., Kudryavtsev I.A., Shevchenko V.E. Study of the effect of curcumin on excision DNA repair in U251 glioblastoma multiforme cells. Uspekhi molekulyarnoy onkologii. 2021;8(4):75-83 (in Russ.). DOI: 10.17650/2313-805X-2021-8-4-75-83. EDN: EPHBXT.

13. Roy S., Rhim J.W. Preparation of antimicrobial and antioxidant gelatin/curcumin composite films for active food packaging application. Colloids Surf B Biointerfaces. 2020;188:110761. DOI: 10.1016/j.colsurfb.2019.110761.

14. Musso Y.S., Salgado P.R., Mauri A.N. Smart edible films based on gelatin and curcumin. Food Hydrocoll. 2017;66:8-15. DOI: 10.1016/j.foodhyd.2016.11.007.

15. Delmar Kю, Bianco-Peled H.Composite chitosan hydrogels for extended release of hydrophobic drugs. Carbohydr Polym. 2016;136:570-580. DOI: 10.1016/j.carbpol.2015.09.072.

16. Facchi S.P., Scariot D.B., Bueno P.V., Souza P.R., Figueiredo L.C., Follmann H.D., Nunes C.S., Monteiro J.P., et al. Preparation and cytotoxicity of N-modified chitosan nanoparticles applied in curcumin delivery.Int J Biol Macromol. 2016;87:237-245. DOI: 10.1016/j.ijbiomac.2016.02.063.

17. Huang S., Wang J., Shang Q. Development and evaluation of a novel polymeric hydrogel of sucrose acrylate-co-polymethylacrylic acid for oral curcumin delivery. J Biomater Sci Polym Ed. 2017;28(2):194-206. Doi: 10.1080/09205063.2016.1262162.

18. Meng R., Wu Z., Xie H.Q., Xu G.X., Cheng J.S., Zhang B. Preparation, characterization, and encapsulation capability of the hydrogel cross-linked by esterified tapioca starch.Int J Biol Macromol. 2020;155:1-5. DOI: 10.1016/j.ijbiomac.2020.03.141.

19. Song S., Wang Z., Qian Y., Zhang L., Luo E. The release rate of curcumin from calcium alginate beads regulated by food emulsifiers. J Agric Food Chem. 2012;60(17):4388-4395. DOI: 10.1021/jf3006883.

20. Osetrov K., Uspenskaya M., Olekhnovich R. The model pH-controlled delivery system based on gelatin-tannin hydrogels containing ferrous ascorbate: iron release in vitro. Biomed Phys Eng Express. 2023;9(2):025010. DOI: 10.1088/2057-1976/acbaa1.

21. Bajpai S.K., Chand N., Ahuja S. Investigation of curcumin release from chitosan/cellulose micro crystals (CMC) antimicrobial films.Int J Biol Macromol. 2015;79:440-448. DOI: 10.1016/j.ijbiomac.2015.05.012.