Effects of the gel containing microcapsules with silver nanoparticles loaded with metronidazole on the state of the gingival microcirculation in animals with experimental periodontitis
https://doi.org/10.24884/1682-6655-2023-22-3-78-85
Abstract
Introduction. Microcirculatory disorders accompany all stages of inflammatory periodontal diseases and their correction is one of the challenges in periodontitis complex therapy. Considering the significance of antibiotic therapy in the treatment of oral cavity inflammatory diseases, the scientific and practical interest lies in studying the possibilities of using a system for targeted delivery of antibacterial agents, as well as its influence on the periodontal tissues microcirculation.The aim of the study is to investigate the effect of a gel containing alginate microcapsules with silver nanoparticles (AgNP) loaded with metronidazole on the state of the gum’s microcirculation in animals with experimental periodontitis. Materials and methods. The study was conducted on 40 white rats. The experimental design involved dividing all animals into several groups: the control group included rats with intact gums; the comparison group were animals with experimental periodontitis; the placebo group were rats with experimental periodontitis treated with a gel containing microcapsules with AgNP but without active components; the experimental group included animals with periodontitis which received applications of the gel containing AgNP microcapsules loaded with metronidazole. Periodontitis was modeled by the ligature method by suturing a multifilament non-absorbable thread in the gum area of the lower jaw incisors. The state of periodontal microcirculation in all presented groups was assessed on the 21st day of the experiment after the ligature removal, using laser Doppler flowmetry. Results. In experimental periodontitis in white rats, the pronounced microcirculatory disorders occur on the 3rd week, manifested by an increase in the perfusion index by 37% as well as an increase in amplitudes of endothelial, neurogenic, myogenic, respiratory, and cardiac perfusion fluctuations compared to the intact control. The gel containing only AgNP microcapsules in rats with periodontitis reduces the perfusion index by 23.9%, without influence on the impaired parameters of active and passive modulation of gingival blood flow. Loading metronidazole into microcapsules with AgNP increases the effectiveness of the gel in the correction of the perfusion index by 6.7% of the amplitudes of myogenic and respiratory fluctuations by 26.8% and 19.8% compared to the analogue without active components. Conclusion. The gel containing microcapsules with AgNP and metronidazole is more effective in restoring gingival perfusion, reducing the amplitudes of myogenic and respiratory oscillations, compared to the analog without active components.
About the Authors
A. A. SavkinaRussian Federation
Savkina Angelina A. – Junior Researcher, Central Research Laboratory
112, Bolshaya Kazachya str., Saratov, 410012
E. V. Lengert
Russian Federation
Lengert Ekaterina V. – Junior Researcher, Central Research Laboratory
112, Bolshaya Kazachya str., Saratov, 410012
A. V. Ermakov
Russian Federation
Ermakov Alexey V. – Junior Researcher, Central Research Laboratory
112, Bolshaya Kazachya str., Saratov, 410012
T. V. Stepanova
Russian Federation
Stepanova Tat’yana V. – Junior Researcher, Central Research Laboratory
112, Bolshaya Kazachya str., Saratov, 410012
A. N. Ivanov
Russian Federation
Ivanov Alexey N. – Doctor of Medical Sciences, Associate Professor, Head, Department of Laboratory Diagnostics, Research Institute of Traumatology, Orthopedics and Neurosurgery; Head, Central Scientific Research Laboratory; Head, Department of Normal Physiology
112, Bolshaya Kazachya str., Saratov, 410012
References
1. Larvin H, Kang J, Aggarwal VR, Pavitt S, Wu J. Risk of incident cardiovascular disease in people with periodontal disease: A systematic review and meta-analysis // Clin Exp Dent Res. 2021;7(1):109–122. Doi: 10.1002/cre2.336.
2. Zhang X, Wang M, Wang X, Qu H, Zhang R, Gu J, Wu Y, Ni T, Tang W, Li Q. Relationship between periodontitis and microangiopathy in type 2 diabetes mellitus: a meta-analysis // J Periodontal Res. 2021;56(6):1019–1027. Doi: 10.1111/jre.12916.
3. Gheorghe DN, Camen A, Popescu DM, Sincar C, Pitru A, Ionele CM, Nicolae FM, Danilescu CM, Roman A, Florescu C. Periodontitis, Metabolic and Gastrointestinal Tract Diseases: Current Perspectives on Possible Pathogenic Connections // J Pers Med. 2022;12(3):341. Doi: 10.3390/jpm12030341.
4. Miklyaev S.V., Leonova O.M., Sushchenko A.V. Analysis of the prevalence of chronic inflammatory diseases of periodontal tissues // Modern problems of science and education. 2018;(2). Available at: https://science-education.ru/ru/article/ view?id=27454. (In Russ.)
5. Zhang J, Yu, J, Dou J, Hu P, Guo Q. The Impact of Smoking on Subgingival Plaque and the Development of Periodontitis: A Literature Review. Front Oral Health. 2021; 2:751099. Doi: 10.3389/froh.2021.751099.
6. Coll PP, Lindsay A, Meng J, Gopalakrishna A, Raghavendra S, Bysani P, O’Brien D. The Prevention of Infections in Older Adults: Oral Health // J Am Geriatr Soc. 2020;68(2): 411–416. Doi: 10.1111/jgs.16154.
7. Eldzharov A, Kabaloeva D, Nemeryuk D, Goncharenko A, Gatsalova A, Ivanova E, Kostritskiy I, Carrouel F, Bourgeois D. Evaluation of Microcirculation, Cytokine Profile, and Local Antioxidant Protection Indices in Periodontal Health, and Stage II, Stage III Periodontitis // J Clin Med. 2021;10(6):1262. Doi: 10.3390/jcm10061262.
8. Bahador A, Ayatollahi B, Akhavan A, Pourhajibagher M, Kharazifard M.J, Sodagar A. Antimicrobial Efficacy of Silver Nanoparticles Incorporated in an Orthodontic Adhesive: An Animal Study // Front Dent. 2020;17(14):1–8. Doi: 10.18502/ fid.v17i14.4177.
9. Yu W-Z, Zhang Y, Liu X, Xiang Y, Li Z, Wu S. Synergistic Antibacterial Activity of Multi Components in Lysozyme/ Chitosan/Silver/Hydroxyapatite Hybrid Coating Mater // Des. 2018;139:351–362.
10. Aurore V, Caldana F, Blanchard M, Kharoubi Hess S, Lannes N, Mantel PY, Filgueira L, Walch M. Silver-nanoparticles increase bactericidal activity and radical oxygen responses against bacterial pathogens in human osteoclasts // Nanomedicine. 2018;14(2):601–607. Doi: 10.1016/j.nano.2017.11.006.
11. Salvioni L, Galbiati E, Collico V, Alessio G, Avvakumova S, Corsi F, Tortora P, Prosperi D, Colombo M. Negatively charged silver nanoparticles with potent antibacterial activity and reduced toxicity for pharmaceutical preparations // Int J Nanomedicine. 2017;12:2517–2530. Doi: 10.2147/IJN. S127799.
12. Ferreyra Maillard APV, Dalmasso PR, López de Mishima BA, Hollmann A. Interaction of green silver nanoparticles with model membranes: possible role in the antibacterial activity // Colloids Surf B Biointerfaces. 2018;171:320–326. Doi: 10.1016/j.colsurfb.2018.07.044.
13. Korolev D, Shumilo M, Shulmeyster G, Krutikov A, Golovkin A, Mishanin A, Spiridonova A, Kulagina O, Galagudza M. Hemolytic Activity, Cytotoxicity, and Antimicrobial Effects of Silver Nanoparticles Conjugated with Lincomycin or Cefazolin // Int J Mol Sci. 2022;23(22):13709. Doi: 10.3390/ ijms232213709.
14. Korolev D, Shumilo M, Shulmeyster G, Krutikov A, Golovkin A, Mishanin A, Gorshkov A, Spiridonova A, Domorad A, Krasichkov A, Galagudza M. Hemolytic Activity, Cytotoxicity, and Antimicrobial Effects of Human Albumin- and Polysorbate-80-Coated Silver Nanoparticles // Nanomaterials (Basel). 2021;11(6):1484. Doi: 10.3390/nano11061484.
15. El-Kamel AH, Ashri LY, Alsarra IA. Micromatricial metronidazole benzoate film as a local mucoadhesive delivery system for treatment of periodontal diseases // AAPS PharmSciTech. 2007;8(3):E75. Doi: 10.1208/pt0803075.
16. Khan G, Yadav SK, Patel RR, Nath G, Bansal M, Mishra B. Development and Evaluation of Biodegradable Chitosan Films of Metronidazole and Levofloxacin for the Management of Periodontitis // AAPS PharmSciTech. 2016; 17(6):1312–1325. Doi: 10.1208/s12249-015-0466-y.
17. Sreeharsha N, Rajpoot K, Tekade M, Kalyane D, Nair AB, Venugopala KN, Tekade RK. Development of Metronidazole Loaded Chitosan Nanoparticles Using QbD Approach-A Novel and Potential Antibacterial Formulation // Pharmaceutics. 2020;12(10):920. Doi: 10.3390/pharmaceutics12100920.
18. Lengert EV, Savkina AA, Ermakov AV, Saveleva MS, Lagutina DD, Stepanova TV, Ivanov AN. Influence of the new formulation based on silver alginate microcapsules loaded with tannic acid on the microcirculation of the experimental periodontitis in rats // Mater Sci Eng C Mater Biol Appl. 2021; 126:112144. Doi: 10.1016/j.msec.2021.112144.
19. Ionel A, Lucaciu O, Moga M et al. Periodontal disease induced in Wistar rats – experimental study // HVM Bioflux. 2015;7(2):90–95.
20. [Krupatkin AI. Fluctuations in blood flow – a new diagnostic language in the study of microcirculation // Regional blood circulation and microcirculation. 2014;13(1):83–99. Doi.org/10.24884/1682-6655-2014-13-1-83-99. (In Russ.). Doi: 10.24884/1682-6655-2014-13- 1-83-99.
21. Savkina AA, Lengert EV, Ermakov AV, Popykhova EB, Stepanova TV, Ivanov AN. Endothelial dysfunctions in experimental periodontitis in white rats // Saratov Scient Med J. 2021;17(4):756–768. (In Russ.)
22. Ren B, Feng Q, He S, Li Y, Fan J, Chai G, Liu L, Liu H, Yang C, Wang Y, Liu H, Liu H, Song Y. VEGF as a potential molecular target in periodontitis: a meta-analysis and microarray data validation // J Inflamm (Lond). 2021;18(1):18. Doi: 10.1186/s12950-021-00281-9.
23. Ionel A, Lucaciu O, Tăbăran F, Berce C, Toader S, Hurubeanu L, Bondor C, Câmpian RS. Histopathological and clinical expression of periodontal disease related to the systemic inflammatory response // Histol Histopathol. 2017; 32(4):379–384. Doi: 10.14670/HH-11-803.
24. Yin IX, Zhang J, Zhao IS, Mei ML, Li Q, Chu CH. The Antibacterial Mechanism of Silver Nanoparticles and Its Application in Dentistry // Int J Nanomedicine. 2020;15:2555–2562. Doi: 10.2147/IJN.S246764.
25. Moaddabi A, Soltani P, Rengo C, Molaei S, Mousavi SJ, Mehdizadeh M, Spagnuolo G. Comparison of antimicrobial and wound-healing effects of silver nanoparticle and chlorhexidine mouthwashes: an in vivo study in rabbits // Odontology. 2022;110(3):577–583. Doi: 10.1007/s10266-022-00690-z.
26. Singh P, Ahn S, Kang JP, Veronika S, Huo Y, Singh H, Chokkaligam M, El-Agamy Farh M, Aceituno VC, Kim YJ, Yang DC. In vitro anti-inflammatory activity of spherical silver nanoparticles and monodisperse hexagonal gold nanoparticles by fruit extract of Prunus serrulata: a green synthetic approach // Artif Cells Nanomed Biotechnol. 2018;46(8):2022– 2032. Doi: 10.1080/21691401.2017.1408117.
27. Orlowski P, Zmigrodzka M, Tomaszewska E, RanoszekSoliwoda K, Czupryn M, Antos-Bielska M, Szemraj J, Celichowski G, Grobelny J, Krzyzowska M. Tannic acid-modified silver nanoparticles for wound healing: the importance of size // Int J Nanomedicine. 2018;13:991–1007. Doi: 10.2147/IJN.S154797.
28. Steckiewicz KP, Cieciórski P, Barcińska E, Jaśkiewicz M, Narajczyk M, Bauer M, Kamysz W, Megiel E, Inkielewicz-Stepniak I. Silver Nanoparticles as Chlorhexidine and Metronidazole Drug Delivery Platforms: Their Potential Use in Treating Periodontitis // Int J Nanomedicine. 2022;17:495–517. Doi: 10.2147/IJN.S339046.
Review
For citations:
Savkina A.A., Lengert E.V., Ermakov A.V., Stepanova T.V., Ivanov A.N. Effects of the gel containing microcapsules with silver nanoparticles loaded with metronidazole on the state of the gingival microcirculation in animals with experimental periodontitis. Regional blood circulation and microcirculation. 2023;22(3):78-85. (In Russ.) https://doi.org/10.24884/1682-6655-2023-22-3-78-85