Hemostatic Gelatin-Alginate Hydrogels Modified with Humic Acids and Impregnated with Aminocaproic Acid

Authors

  • Vladimir Lebedev The Department of Plastics and Biologically Active Polymers Technology, National Technical University «Kharkiv Polytechnic Institute», 2, Kyrpychova str., 61002 Kharkiv, Ukraine https://orcid.org/0000-0001-6934-2349
  • Volodymyr Kopach Department of Micro- and Nanoelectronics, National Technical University «Kharkiv Polytechnic Institute», 2, Kyrpychova str., 61002 Kharkiv, Ukraine
  • Liudmyla Maloshtan The Common Pharmacy Department, National Technical University «Kharkiv Polytechnic Institute», 2, Kyrpychova str., 61002 Kharkiv, Ukraine https://orcid.org/0000-0003-1904-9579
  • Ihor Hrubnyk The Common Pharmacy Department, National Technical University «Kharkiv Polytechnic Institute», 2, Kyrpychova str., 61002 Kharkiv, Ukraine
  • Аnzhela Olkhovska The Department of Organizations and Management Healthcare and Social Medicine, National Technical University «Kharkiv Polytechnic Institute», 2, Kyrpychova str., 61002 Kharkiv, Ukraine https://orcid.org/0000-0002-0237-5741
  • Sergiy Bogatyrenko Faculty of Physics, V.N. Karazin Kharkiv National University, 4, Svobody Square, 61022, Kharkiv, Ukraine https://orcid.org/0000-0002-6044-6886
  • Sergey Petrushenko Faculty of Physics, V.N. Karazin Kharkiv National University, 4, Svobody Square, 61022, Kharkiv, Ukraine and Technical University of Liberec, 2, Studentska str., 46117, Liberec, Czech Republic Technical University of Liberec, 46117 Liberec, Czech Republic https://orcid.org/0000-0002-7727-9527
  • Аnna Cherkashina The Department of Plastics and Biologically Active Polymers Technology, National Technical University «Kharkiv Polytechnic Institute», 2, Kyrpychova str., 61002 Kharkiv, Ukraine
  • Katerina Lebedeva The Department of Plastics and Biologically Active Polymers Technology, National Technical University «Kharkiv Polytechnic Institute», 2, Kyrpychova str., 61002 Kharkiv, Ukraine
  • Natalja Klochko Department of Micro- and Nanoelectronics, National Technical University «Kharkiv Polytechnic Institute», 2, Kyrpychova str., 61002 Kharkiv, Ukraine https://orcid.org/0000-0002-0852-4373

DOI:

https://doi.org/10.6000/1929-5995.2024.13.05

Keywords:

Hemostasis, biopolymer hydrogel, swelling, thermo-responsivity, drug delivery, X-ray diffractometry, Fourier transform infrared spectroscopy, transmembrane transport

Abstract

The work is devoted to the development of safe and biocompatible multicomponent gelatin-alginate hydrogels modified with humic acids (HA) and impregnated with the antifibrinolytic agent aminocaproic acid (АА).These hydrogels are designed to be effective hemostatic materials with anti-inflammatory properties and the ability to deliver in less than 30 seconds to deep and hidden areas of hemorrhages. Studies of the crystal structure by X-ray diffraction analysis and non-covalent interactions of molecules by Fourier transform infrared spectroscopy of the developed hemostatic gelatin-alginate hydrogels modified with bactericidal and anti-inflammatory humic acids made it possible to identify the optimal concentrations of HA from 2.5 wt.%. up to 5 wt.%. At such concentrations of HA, gelatin-alginate hydrogels have a semicrystalline structure. Due to non-covalent bonds between polymer chains, they are thermo-responsive with a gel-sol transition temperature of about 37 °C. Impregnation of these hydrogels with aminocaproic acid led to an almost threefold increase in their swelling, which facilitated the dissolution of AA in the hydrogels and its subsequent delivery to the wound. Experiments simulating the transmembrane transport of aminocaproic acid from the developed gelatin-alginate hydrogels confirmed their ability to rapidly deliver up to 494± 3 mg of AA from 5 ml of hydrogel to the wound.

References

Chen X-J, Lei Z-Y, Liu P, et al. An aminocaproic acid-grafted chitosan derivative with superior antibacterial and hemostatic properties for the prevention of secondary bleeding. Carbohydrate Polymers 2023; 316: 120988-11. https://doi.org/10.1016/j.carbpol.2023.120988

Li Q, Hu E, Yu K, et al. Self-propelling Janus particles for hemostasis in perforating and irregular wounds with massive hemorrhage. Adv. Funct. Mater 2020; 30(42): 2004153-13. https://doi.org/10.1002/adfm.202004153

Zhong Y, Hu H, Min N, et al. Application and outlook of topical hemostatic materials: A narrative review. Ann Transl Med 2021; 9(7): 577-20. https://doi.org/10.21037/atm-20-7160

Jiao S, Zhang X, Cai H, et al. Recent advances in biomimetic hemostatic materials. Materials Today Bio 2023; 19: 100592-22. https://doi.org/10.1016/j.mtbio.2023.100592

Yang X, Wang X, Gao X, et al. What else should hemostatic materials do beyond hemostasis: A review. Materials Today Bio 2024; 25: 101008-18. https://doi.org/10.1016/j.mtbio.2024.101008

Ghimire S, Sarkar P, Rigby K, et al. Polymeric materials for hemostatic wound healing. Pharmaceutics 2021; 13: 2127-27. https://doi.org/10.3390/pharmaceutics13122127

Yu P, Zhong W. Hemostatic materials in wound care. Burns & Trauma 2021: 9; tkab019-17. https://doi.org/10.1093/burnst/tkab019

Peng X, Xu X, Deng Y, et al. Ultrafast self‐gelling and wet adhesive powder for acute hemostasis and wound healing. Adv. Funct. Mater 2021; 31(33): 2102583-13. https://doi.org/10.1002/adfm.202102583

Xie Y, Gao P, He F et al.Application of alginate-based hydrogels in hemostasis Gels 2022; 8: 109-21. https://doi.org/10.3390/gels8020109

Fatimi A. Cellulose-Based Hydrogels: Patent Analysis. Journal of Research Updates in Polymer Science 2022; 11: 16–24. https://doi.org/10.6000/1929-5995.2022.11.03

Karim MM, Lasker T, et al. Low-Cost Production of Chitosan Biopolymer from Seafood Waste: Extraction and Physiochemical Characterization. Journal of Research Updates in Polymer Science 2024; 13: 17–26. https://doi.org/10.6000/1929-5995.2024.13.03

Du Y, Li L, Peng H, et al. A spray-filming self-healing hydrogel fabricated from modified sodium alginate and gelatin as a bacterial barrier. Macromol. Biosci 2020; 20: 1900303-11. https://doi.org/10.1002/mabi.201900303

Xi G, Liu W, Chen M, et al. Polysaccharide-based lotus seedpod surface-like porous microsphere with precise and controllable micromorphology for ultrarapid hemostasis. ACS Appl. Mater. Interfaces 2019; 11: 46558−46571. https://doi.org/10.1021/acsami.9b17543

Mecwan M, Li J, Falcone N, et al. Recent advances in biopolymer-based hemostatic materials. Regenerative Biomaterials 2022; 9: rbac063-26. https://doi.org/10.1093/rb/rbac063

Venezia V, Avallone PR, Vitiello G, et al. Adding humic acids to gelatin hydrogels: a way to tune gelation. Biomacromolecule 2022; 23(1): 443–453. https://doi.org/10.1021/acs.biomac.1c01398

Zeigler ZR. Effects of epsilon aminocaproic acid on primary hemostasis. Haemostasis 1991; 21(5): 313–320. https://doi.org/10.1159/000216242

Heidmann P, Tornquist SJ, Qu A, et al. Laboratory measures of hemostasis and fibrinolysis after intravenous administration of -aminocaproic acid in clinically normal horses and ponies. AJVR 2005; 66(2): 313–318. https://doi.org/10.2460/ajvr.2005.66.313

Wilson JM, Bower LK, Fackler JC, Beals DA, Bergus BO, Kevy SV. Aminocaproic acid decreases the incidence of intracranial hemorrhage and other hemorrhagic complications of ECMO. Journal of Pediatric Surgery 1993; 28(4): 536–540. https://doi.org/10.1016/0022-3468(93)90612-O

Lebedev V, Miroshnichenko D, Tykhomyrova T, et al. Design and research of environmentally friendly polymeric materials modificated by derivatives of coal. Petroleum and Coal 2023; 65(2): 334-340. https://doi.org/10.1063/5.0119925

Lebedev V, Miroshnichenko D, Vytrykush N, et al. Novel biodegradable polymers modified by humic acids. Materials Chemistry and Physics 2024; 313: 128778. https://doi.org/10.1016/j.matchemphys.2023.128778

Lebedeva KO, Cherkashina AM, Tykhomyrova TS, et al. Design and researching of biologically active polymeric hydrogel transdermal materials modified by humic acid. IOP Conference Series: Earth and Environmental Science 2023; 1254(1): 012009. https://doi.org/10.1088/1755-1315/1254/1/012009

Lebedeva K, Cherkashina A, Voronkin A, et al. Design and researching smart biologically active polymeric hydrogel transdermal nanomaterial’s. 2023 IEEE 4th KhPI Week on Advanced Technology (KhPIWeek) 2023: 1–5. https://doi.org/10.1109/KhPIWeek61412.2023.10312985

Lebedeva K, Cherkashina А, Masikevych YG, et al. Modeling of Smart Bio-Medical Active Polymeric Hydrogel Transdermal Materials. Journal of Engineering Sciences 2024; 11(1): C1 - C7. https://doi.org/10.21272/jes.2024.11(1).c1

Miroshnichenko D, Lebedeva K, Cherkashina A, et al. Study of hybrid modification with humic acids of environmentally safe biodegradable hydrogel films based on hydroxypropyl methylcellulose. C- Journal of carbon research 2022; 8: 71–10. https://doi.org/10.3390/c8040071

Perkasa DP, Erizal E, Purwanti T, et al. Characterization of semi-interpenetrated network alginate/gelatin wound dressing crosslinked at sol phase. Indonesian Journal of Chemistry 2018; 18(2): 367–375. https://doi.org/10.22146/ijc.25710

Uttayarat P, Chiangnoon R, Eamsiri J, et al. Processing and characterization of antibacterial hydrogel sheet dressings composed of poly(vinyl alcohol) and silk fibroin for wound healing application. Walailak J Sci & Tech 2019; 16(5): 349-359. https://doi.org/10.48048/wjst.2019.6292

Klochko NP, Barbash VA, Petrushenko SI, et al. Thermoelectric textile devices with thin films of nanocellulose and copper iodide. Journal of Materials Science: Materials in Electronics 2021; 32: 23246–23265. https://doi.org/10.1007/s10854-021-06810-9

Lan L, Ping J, Xiong J, et al. Sustainable natural bio-origin materials for future flexible devices. Adv. Sci. 2022; 9(15): 2200560–34. https://doi.org/10.1002/advs.202200560

Sundarrajan P, Eswaran P, Marimuthu A, et al. One pot synthesis and characterization of alginate stabilized semiconductor nanoparticles”. Bull. Korean Chem. Soc. 2012; 33(10): 3218–3224. https://doi.org/10.5012/bkcs.2012.33.10.3218

Ghosh D, Pramanik A, Sikdar N, et al. Synthesis of low molecular weight alginic acid nanoparticles through persulfate treatment as effective drug delivery system to manage drug resistant bacteria”, BiotechnolBioproc E 2011; 16: pp. 383-392. https://doi.org/10.1007/s12257-010-0099-7

Bhagyaraj S, Krupa I. Alginate-mediated synthesis of hetero-shaped silver nanoparticles and their hydrogen peroxide sensing ability. Molecules 2020; 25: 435-10. https://doi.org/10.3390/molecules25030435

Radev L, Fernandes M, Salvado I, et al. Organic/inorganic bioactive materials Part III: in vitro bioactivity of gelatin/silicocarnotite hybrids. Open Chemistry 2009; 7(4): 721-730. https://doi.org/10.2478/s11532-009-0078-z

Wang K, Wang W, Ye R, et al. Mechanical and barrier properties of maize starch-gelatin composite films: effects of amylose content. J Sci Food Agric. 2017; 97(11): 3613-3622. https://doi.org/10.1002/jsfa.8220

Koesnarpadi S, Santosa SJ, Siswanta D, et al. Synthesis and characterization of magnetite nanoparticle coated humic acid (Fe3O4/HA). Procedia Environmental Sciences 2015; 30: 103 – 108. https://doi.org/10.1016/j.proenv.2015.10.018

Derkach SR, Voron’ko NG, Sokolan NI, et al. Interactions between gelatin and sodium alginate: UV and FTIR studies. Journal of Dispersion Science and Technology 2019; 5: 690-698. https://doi.org/10.1080/01932691.2019.1611437

Galante R, Pinto TJA, Colaço R, et al. Sterilization of hydrogels for biomedical applications: A review. J Biomed Mater Res Part B 2018; 106(6): 2472-2492. https://doi.org/10.1002/jbm.b.34048

Stoppel WL, White JC, Horava SD, et al. Terminal sterilization of alginate hydrogels: Efficacy and impact on mechanical properties. J Biomed Mater Res Part B 2014; 102Ba: 877–884. https://doi.org/10.1002/jbm.b.33070

Zhang F, Scull G, Gluck JM, et al. Effects of sterilization methods on gelatin methacryloyl hydrogel properties and macrophage gene expression in vitro. Biomed Mater. 2022; 18(1): 10-27. https://doi.org/10.1088/1748-605X/aca4b2

Carranza T, Zalba- Balda M, BarriolaBaraibar MJ, et al. Effect of sterilization processes on alginate/gelatin inks for three-dimensional printing. Int J Bioprint, 2023; 9(1): 309-319. https://doi.org/10.18063/ijb.v9i1.645

Downloads

Published

2024-08-05

How to Cite

Lebedev, V. ., Kopach, V. ., Maloshtan, L. ., Hrubnyk, I. ., Olkhovska А. ., Bogatyrenko, S. ., Petrushenko, S. ., Cherkashina А. ., Lebedeva, K. ., & Klochko, N. . (2024). Hemostatic Gelatin-Alginate Hydrogels Modified with Humic Acids and Impregnated with Aminocaproic Acid. Journal of Research Updates in Polymer Science, 13, 34–44. https://doi.org/10.6000/1929-5995.2024.13.05

Issue

Section

Articles

Most read articles by the same author(s)