Abstract
Objective of the study – creation of dressings based on high molecular weight polyvinylpyrrolidone (PVP) and experimental evaluation of the hemostatic activity of local dressings in vivo and in vitro.
Material and methods. We used 2.6, 6.4 and 12.8% solutions of polyvinylpyrrolidone with a molecular weight of 2.0–4.5 MDa in distilled water. On the basis of these solutions, samples of sponge-shaped dressings were prepared. Scanning electronic microscopy was performed to study the structure of the dressings. In vivo hemostatic activity was determined by the time of stopping bleeding and the volume of blood loss. The influence of the interaction of the contact surface of the coatings with blood in vitro was assessed by the results of counting the number of platelets and determining the level of fibrinogen in blood plasma. An integral assessment of the hemostatic system was performed using thromboelastometry and a thrombin generation test in blood plasma.
Results. In experiments in vivo, sponge-shaped dressings based on a 12.8% PVP solution (70.93 ± 16.43%) exhibited high hemostatic activity. After their contact with blood, the number of platelets decreased by 1.22 times, and there was a decrease in the generation of thrombin in plasma by an average of 1.27 times compared with the control. According to the data of scanning electronic microscopy, the pore size of the coatings was from 10 to 60 μm. Samples of coatings based on 2.6 and 6.4% PVP aqueous solutions had low hemostatic activity (26.69 ± 6.80 and 27.86 ± 7.79%, respectively) and did not affect the content of the main blood coagulation substrates, thromboelastometry parameters. and a thrombin generation test.
Conclusion. The performed study revealed a direct dependence of the increase in the hemostatic activity of the created dressings on the increase in the mass fraction of polyvinylpyrrolidone in the solution. According to the data of scanning electronic microscopy, the dressings had a porous-cellular structure with different pore sizes, which is important when additional pharmacologically active substances are introduced into the sponge. Analysis of the results of in vitro experiments confirmed a sharp decrease in the number of platelets upon contact of the dressings with blood.
References
- Mayorova A.V., Syisuev B.B., Hanalieva I.A., Vihrova I.V. Modern assortment, properties and perspectives of medical dressings improvement of wound treatment. Pharmacy & Pharmacology. 2018; 6 (1): 4–32 (in Russ.). DOI: 10.19163/2307-9266-2018-6-1-4-32
- Welch M., Barratt J., Peters A., Wright C. Systematic review of prehospital haemostatic dressings. J. R. Army Med. Corps. 2019; Published Online First: 2 February 2019. DOI: 10.1136/jramc-2018-001066
- Iliescu Nelea M., Paek L., Dao L., Rouchet N., Efanov J.I.., Édouard C. et al. In-situ characterization of the bacterial biofilm associated with XeroformTM and KaltostatTM dressings and evaluation of their effectiveness on thin skin engraftment donor sites in burn patients. Burns. 2019; 45 (5): 1122–30. DOI: 10.1016/j.burns.2019.02.024
- Hwang J.J., Hong S.J., Han J.P., Ko B.M., Lee T.H., Lee J.S. Efficacy of Surgicel® (Fibrillar) for preventing bleeding after endoscopic submucosal dissection for gastric epithelial tumors. J. Dig. Dis. 2018; 19 (11): 657–63. DOI: 10.1111/1751-2980.12672
- Mot’ková P., Brozˇková I., Vytrˇasová J., Kukla R. Antimicrobial effect of OKCEL® H-D prepared from oxidized cellulose. Folia Microbiol (Praha). 2018; 63 (1): 57–62. DOI: 10.1007/s12223-017-0534-7
- Gilbert D.R., Angell J., Abaza R. Evaluation of absorbable hemostatic powder for prevention of lymphoceles following robotic prostatectomy with lymphadenectomy. Urology. 2016; 98: 75–80. DOI: 10.1016/j.urology. 2016.06.071
- Wells C.I., Ratnayake C.B.B., Mentor K., Sen G., Hammond J.S., French J.J. et al. Haemostatic efficacy of topical agents during liver resection: A network metaanalysis of randomised trials. World J. Surg. 2020; 44 (10): 3461–9. DOI: 10.1007/s00268-020-05621-z
- Bracey A., Shander A., Aronson S., Boucher B.A., Calcaterra D., Chu M.W.A. et al. The use of topical hemostatic agents in cardiothoracic surgery. Ann. Thorac. Surg. 2017; 104 (1): 353–60. DOI: 10.1016/j.athoracsur.2017.01.096
- Li J., Celiz A.D., Yang J., Yang Q., Wamala I., Whyte W. et al. Tough adhesives for diverse wet surfaces. Science. 2017; 357 (6349): 378–81. DOI: 10.1126/science.aah6362
- Nikolian V.C., Alam H.B. The next generation of hemorrhage therapy. In: front line surgery. Cham: Springer International Publishing; 2017: 775–86. DOI: 10.1007/978-3-319-56780-8_45
- Bouten P.J.M., Zonjee M., Bender J., Yauw S.T.K., van Goor H., van Hest J.C.M. et al. The chemistry of tissue adhesive materials. Prog. Polym. Sci. 2014; 39 (7): 1375–405. DOI: 10.1016/j.progpolymsci.2014.02.001
- Kamoun E.A., Kenawy E.-R.S., Chen X. A review on polymeric hydrogel membranes for wound dressing applications: PVA-based hydrogel dressings. J. Adv. Res. 2017; 8 (3): 217–33. DOI: 10.1016/j.jare.2017.01.005
- Lipatov V.A., Sotnikov K.A., Severinov D.A., Ershov M.P. To the issue of methodology of comparative study of the degree of hemostatic activity of topical hemostatic agents. Surgery News. 2018; 26 (1): 81–95 (in Russ.). DOI: 10.18484/2305-0047.2018.1.81
- Wang L., You X., Dai C., Tong T., Wu J. Hemostatic nanotechnologies for external and internal hemorrhage management. Biomater. Sci. 2020; 8 (16): 4396–412. DOI: 10.1039/D0BM00781A
- Kurakula M., Rao G.S.N.K. Pharmaceutical assessment of polyvinylpyrrolidone (PVP): As excipient from conventional to controlled delivery systems with a spotlight on COVID-19 inhibition. J. Drug. Deliv. Sci Technol. 2020; 60: 102046. DOI: 10.1016/j.jddst.2020.102046
- Аракелян А.Г., Кочуров Д.В., Паламарчук А.А., Шишакина О.А. Полимерсодержащие кровезаменители. Тенденции развития науки и образования. 2018; 44: 45–6. DOI: 10.18411/lj-11-2018-183 [Arakelyan A.G., Kochurov D.V., Palamarchuk A.A., Shishakina O.A. Polymer blood substitutes. Trends of Development of Science and Education. 2018; 44: 45–6 (in Russ.). DOI: 10.18411/lj-11-2018-183
- Nikolaeva L.L., Gulyakin I.D., Oborotova N.A., Bunyatyan N.D. Analysis polyvinylpyrrolidone in dosage forms. Pharmacy & Pharmacology. 2016; 4 (2, 15): 88–94 (in Russ.).
- Barba B.J.D., Tranquilan-Aranilla C., Abad L.V. Hemostatic potential of natural/synthetic polymer based hydrogels crosslinked by gamma radiation. Radiat. Phys. Chem. 2016; 118: 111–3. DOI: 10.1016/j.radphyschem.2015.02.022
- Polymeric materials of the “Polydon” series. Available at: http://robell.group/polidon.html (accessed May 26, 2021) (in Russ.).
- Mironov А.N. (Ed.). A guide to preclinical drug research. Part one. Moscow; 2012 (in Russ.).
- Hemker H.C., Giesen P., Al Dieri R., Regnault V., de Smedt E., Wagenvoord R. et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol. Haemost. Thromb. 2003; 33 (1): 4–15. DOI: 10.1159/00007163
About the authors
- Valeriy A. Kabak, Manager, ORCID
- Dmitriy Yu. Bychichko, Physician-Biochemist, Junior Researcher, ORCID
- Galina G. Belozerskaya, Dr. Med. Sc., Head of Laboratory, ORCID
- Andrey P. Momot, Dr. Med. Sc., Professor, Director of the Altai Branch, ORCID
- Marina V. Pykhteeva, Physician-Laboratory Assistant, ORCID
- Ol’ga E. Nevedrova, Cand. Biol. Sc., Senior Researcher, ORCID
- Asaf R. Lempert, Cand. Med. Sc., Researcher, ORCID
- Yuliya S. Logvinova, Cand. Med. Sc., Senior Researcher, Physician-Biochemist, ORCID
- Aleksandr A. Sivkov, Dr. Tech. Sc., Professor of Department, School of Energy Engineering, ORCID
- Ivan I. Shanenkov, Cand. Tech. Sc., Associate Professor of Department, ORCID
- Evgeniy M. Golubev, Head of Department, ORCID
- Tat’yana I. Shirokova, Deputy Head of Department, ORCID
- Maksim S. Mironov, Laboratory Assistant, ORCID
- Акопян Людмила Владимировна, канд. мед. наук, ассистент кафедры оториноларингологии, ORCID