Influence of the Ratio of Antibacterial and AntiInflammatory Components on the Effectiveness of Gels in Correcting Gingival Microcirculation Disorders in Animals with Experimental Periodontitis

Introduction. Microcirculation disorders accompanying the inflammatory response to periodontopathogenic microflora are a key element in the pathogenesis of periodontitis. The complex therapy of periodontitis includes the administration of antibacterial and anti-inflammatory drugs, which can be optimized through modern microencapsulation technologies that allow creating dosage forms combining different classes of drugs. In this regard, optimization of the ratio of antibacterial and antiinflammatory agents in multi-target drugs is of not only scientific but also practical interest. The aim of the study was to investigate the effect of a range of experimental gel samples with different ratios of microcapsules containing anti-inflammatory and antibacterial substances on the state of the gingival microcirculatory bed in animals with experimental periodontitis. Materials and methods. The studies were carried out on 50 white rats. The experimental design involved dividing all animals into several groups: control (rats with intact gingiva); comparison group (animals with experimental periodontitis); experimental groups № 1, № 2, № 3 (rats with experimental periodontitis treated with a gel containing microcapsules with AgNPs loaded with an equal ratio of tannic acid and metronidazole (1:1), a predominance of capsules with tannic acid (2:1) and a predominance of metronidazole capsules (1:2), respectively). Periodontitis was modeled using the ligature method by suturing a polyfilament non-absorbable thread into the gums in the area of the lower jaw incisors. The state of the microcirculation in all presented groups was assessed using laser Doppler flowmetry after removal of the ligature on the 21st day of the experiment. Results. It has been established that gel applications containing an equal amount of active substances effectively reduce the increased perfusion rate by 30% and partially correct the parameters of active and passive blood flow modulation in rats with experimental periodontitis. A gel with a predominance of antibacterial components reduces the perfusion index by 23%, but does not ensure the restoration of active and passive modulation of gingival blood flow in white rats with experimental periodontitis. The use of the gel, in which the anti-inflammatory component predominates ensures complete restoration of gingival microcirculation in animals with periodontitis. The gel with a predominance of anti-inflammatory components exceeds the analogue with an equal ratio of capsules with active substances in the correction of cardiac oscillations by 39%, as well as the analogue with a predominance of antibacterial components in the effectiveness of perfusion correction by 4%, myogenic by 38%, neurogenic by 27%, respiratory by 1.3 times and cardiac oscillations by 1.4 times. Conclusions. Gels containing microcapsules with tannic acid and metronidazole significantly correct gingival perfusion disorders and its modulation mechanisms in rats with experimental periodontitis. The efficiency of correction of microcirculatory disorders in animals with periodontitis depends on the ratio of antibacterial and anti-inflammatory components in the gel. The use of a gel sample containing capsules with tannic acid and metronidazole in a ratio of 2:1 in rats with experimental periodontitis ensures complete restoration of gingival microcirculation.

1. Gimranova IA, Khakimova LR, Akmalova GМ, Gazizullina GR. Modern methods of diagnosis of periodontal diseases: opportunities and prospects (review of literature). Klinicheskaya Laboratornaya Diagnostika. 2023;68(9):570-577. (In Russ.)]. https://doi.org/10.51620/0869-2084-2023-68-9-570-577.

2. Alieva MS, Rasulov IM, Magomedov MA, Meylanova RD. Modern aspects of etiology and pathogenesis of parodontitis. Izvestija Dagestanskogo gosudarstvennogo pedagogicheskogo universiteta. Estestvennye i tochnye nauki. 2013;1(22):25-29. (In Russ.)].

3. Savkina AA, Lengert EV, Ermakov AV, et al. Changes in the concentration of markers of endothelial dysfunction and bone resorption in the treatment of experimental periodontitis using a gel containing metronidazoleloaded silver alginate microcapsules. Journal of new medical technologies. 2024;31(3):130-133. (In Russ.)]. https://doi.org/10.24412/1609-2163-2024-3-130-133.

4. Savkina AA, Lengert EV, Ermakov AV, et al. The influence of combined loading of antibacterial and anti-inflammatory components into microcapsules with silver nanoparticles on the effectiveness of the gel in correcting key links in the pathogenesis of periodontitis. Patogenez [Pathogenesis]. 2024;22(2):13-20. (In Russ.)]. https://doi.org/10.25557/2310-0435.2024.02.13-20.

5. Savkina AA, Lengert EV, Ermakov AV, et al. 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 hemodynamics and microcirculation. 2023;22(3):78-85. (In Russ.)]. https://doi.org/10.24884/1682-6655-2023-22-3-78-85.

6. Ionel A, Lucaciu O, Moga M, et al. Periodontal disease induced in Wistar rats experimental study. HVM Bioflux. 2015;7(2):90-95.

7. Lengert EV, Savkina AA, Ermakov AV, et al. 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. https://doi.org/10.1016/j.msec.2021.112144.

8. Humeau A, Koïtka A, Abraham P, et al. Time-frequency analysis of laser Doppler flowmetry signals recorded in response to a progressive pressure applied locally on anaesthetized healthy rats. Phys Med Biol. 2004;49(5):843-857. https://doi.org/10.1088/0031-9155/49/5/014.

9. Ravaeva MY, Chuyan EN, Cheretaev IV, et al. Tissue microhemodynamic indices in rats exposed to acetylsalicylic acid and metal salicylates. J Evol Biochem Phys. 2021;57:75-87. https://doi.org/10.1134/S0022093021010075.

10. Curuțiu C, Dițu LM, Grumezescu AM, Holban AM. Polyphenols of Honeybee Origin with Applications in Dental Medicine. Antibiotics (Basel). 2020;9(12):856. https://doi.org/10.3390/antibiotics9120856.

11. Palaska I, Papathanasiou E, Theoharides TC. Use of polyphenols in periodontal inflammation. Eur J Pharmacol. 2013; 720(1-3):77-83. https://doi.org/10.1016/j.ejphar.2013.10.047.

12. Jayusman PA, Nasruddin NS, Mahamad Apandi NI, et al. Therapeutic Potential of Polyphenol and Nanoparticles Mediated Delivery in Periodontal Inflammation: A Review of Current Trends and Future Perspectives. Front Pharmacol. 2022;13:847702. Published 2022 Jul 12. https://doi.org/10.3389/fphar.2022.847702.

13. Muthuraj MSA, Janakiram S, Chithresan K. Systemic Metronidazole in the Treatment of Periodontitis. SunText Rev Dental Sci. 2020;1(4):124. https://doi.org/10.51737/2766-4996.2020.024.

14. Martinez-Gutierrez F, Boegli L, Agostinho A, et al. Anti-biofilm activity of silver nanoparticles against different microorganisms. Biofouling. 2013;29(6):651-660. https://doi.org/10.1080/08927014.2013.794225.

15. Steckiewicz KP, Cieciórski P, Barcińska E, et al. Silver Nanoparticles as Chlorhexidine and Metronidazole Drug Delivery Platforms: Their Potential Use in Treating Periodontitis. Int J Nanomedicine. 2022;17:495-517. https://doi.org/10.2147/IJN.S339046.