Efficacy of Controlled-Release Combination of Novel Amoxicillin and Metronidazole Nanoparticles in Experimental Periodontitis: An in Vivo Study

Volume 11 , Issue 2 , August 2024 , Pages 53-65

Authors

Nabaz Y. Hussein 1 ; Sarhang S. Gul 1 ; Sadat A. Aziz 1

1 University of Sulaimani

DOI logo 10.17656/sdj.10192

Keywords

Abstract

Objective: This study was formulated to examine the efficacy of a novel gel incorporating nanoparticles of amoxicillin and metronidazole as an adjunctive to periodontal treatment on periodontal clinical parameters.
Methods: Fifty-eight healthy male rats were used in the study. The study design includes five groups: Group 1 Baseline (Day 0): normal rats without periodontitis induction or treatment. Group 2: untreated induced periodontitis (IP); Group 3 (negative control): Scaling and root surface debridement (RSD) with chitosan gel: Group 4: Positive control: using the (1.5%) gel of the microparticle combination of amoxicillin and metronidazole; Group 5: Test group: applying the nanoparticle gel (1.5%). Experimental periodontitis was induced by ligating a silk suture around the cervical area of the lower central incisor. Periodontal clinical parameters, including gingival index (GI), alveolar bone level (ABL) (mm), bleeding index (BI), mobility index (MI), and periodontal pocket depth (PPD) (mm), were measured after 2 and 4 weeks.
Results: The novel nanoparticle combination of amoxicillin and metronidazole gel significantly improved periodontal clinical parameters of GI (2.33 ± 0.51 to 1 ± 0.63), BI (%) (76.20% ± 1.52 to 43% ± 2.21), MI (2.16 ± 0.40 to 0.66 ± 0.51), and PPD (mm) (0.81 ± 0.049mm to 0.49 ± 0.056mm) at two weeks following IP induction. However, the microparticle combination of amoxicillin and metronidazole only significantly improved MI and PPD (P<0.05). BI, MI, and PPD improved significantly in groups 4 and 5 compared to group 2 at 4 weeks.
Conclusions: These study results suggest that the novel nanoparticle gel significantly improved periodontal clinical parameters when used in this therapeutic modality.

References

  1. Van Dyke TE. Control of inflammation and periodontitis. Periodontol 2000. 2007;45(1):158-66.
  2. Zhang Z, Liu D, Liu S, Zhang S, Pan Y. The Role of Porphyromonas gingivalis outer membrane vesicles in periodontal disease and related systemic diseases. Front Cell Infect Microbiol. 2021;10(58):58-9.
  3. Pan W, Wang Q, Chen Q. The cytokine network involved in the host immune response to periodontitis. Int J Oral Sci. 2019;11(3):1-13.
  4. Hajishengallis G, Lamont RJ. Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology. Mol Oral Microbiol. 2012;27(6):409-19.
  5. Tanwar J, Hungund S, Dodani K. Nonsurgical periodontal therapy: A review. J Oral Res Rev. 2016;8(1):39-44.
  6. Slots J. Selection of antimicrobial agents in periodontal therapy. J Periodontal Res. 2002;37(5):389-98.
  7. Feres M, Retamal-Valdes B, Mestnik MJ, de Figueiredo LC, et al. The ideal time of systemic metronidazole and amoxicillin administration in the treatment of severe periodontitis: study protocol for a randomized controlled trial. Trials. 2018;19(1):201.
  8. Eickholz P, Koch R, Göde M, Nickles K, Kocher T, Lorenz K, et al. Clinical benefits of systemic amoxicillin/metronidazole may depend on periodontitis stage and grade: An exploratory sub-analysis of the abparo trial. J Clin Periodontol. 2023;50(9):1239-52.
  9. Nair SC, Anoop KR. Intraperiodontal pocket: An ideal route for local antimicrobial drug delivery. J Adv Pharm Technol Res. 2012;3(1):9-15.
  10. Sholapurkar A, Sharma D, Glass B, Miller C, Nimmo A, Jennings E. Professionally delivered local antimicrobials in the treatment of patients with periodontitis—a narrative review. Dent J. 2021;9(1):2.
  11. Joshi D, Garg T, Goyal AK, Rath G. Advanced drug delivery approaches against periodontitis. Drug Deliv. 2016;23(2):363-77.
  12. Michalowicz BS, Pihlstrom BL, Drisko CL, Cobb CM, Killoy WJ, et al. Evaluation of periodontal treatments using controlled-release tetracycline fibers: maintenance response. J Periodontol. 1995;66(8):708-15.
  13. Rajeshwari H, Dhamecha D, Jagwani S, Rao M, et al. Local drug delivery systems in the management of periodontitis: A scientific review. J Control Release. 2019;30(7):393-409.
  14. Sowmya S, Bumgardener JD, Chennazhi KP, Nair SV, Jayakumar R. Role of nanostructured biopolymers and bioceramics in enamel, dentin and periodontal tissue regeneration. Prog Polym Sci. 2013;(38):1748-72.
  15. Fischer RG, Klinge B. Clinical and histological evaluation of ligature-induced periodontitis in the domestic ferret. J Clin Periodontol. 1994;21(4):230-9.
  16. Verzelleti GN, Gaio EJ, Linhares DS, Rösing CK. Effect of obesity on alveolar bone loss in experimental periodontitis in Wistar rats. J Appl Oral Sci. 2012;20(2):218-21.
  17. Ionel A. Periodontal disease induced in Wistar rats - experimental study. HVM Bioflux. 2015;7(2):90-91.
  18. Azeez SH, Gaphor SM, Sha AM, Garib BT. Effect of Pistacia atlantica subsp. kurdica Gum in experimental periodontitis induced in wistar rats by utilization of osteoclastogenic bone markers. Molecules. 2020;25(24):5819.
  19. Sha AM, Garib BT, Azeez SH, Gul SS. Effects of curcumin gel on osteoclastogenic bone markers in experimental periodontitis and alveolar bone loss in Wistar rats. J Dent Sci. 2021;16(3):905-14.
  20. Uslu MÖ, Eltas A, Marakoğlu İ, Dündar S, Şahin K, Özercan İH. Effects of diode laser application on inflammation and mpo in periodontal tissues in a rat model. J Appl Oral Sci. 2018;26(13):3-6.
  21. Grimard BA, Hoidal MJ, Mills MP, Mellonig JT, Nummikoski PV, Mealey BL. Comparison of clinical, periapical radiograph, and cone-beam volume tomography measurement techniques for assessing bone level changes following regenerative periodontal therapy. J Periodontol. 2009;80(1):48-55.
  22. Yağan A, Kesim S, Liman N. Effect of Low-Dose Doxycycline on Serum Oxidative Status, Gingival Antioxidant Levels, and Alveolar Bone Loss in Experimental Periodontitis in Rats. J Periodontol. 2014;85(3):478-89.
  23. Komatsu K, Yamazaki Y, Yamaguchi S, Chiba M. Comparison of biomechanical properties of the incisor periodontal ligament among different species. J Anat Rec. 1998;250(4):408-17.
  24. Tonetti MS, Greenwell H. Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. J Periodontol. 2018;89(8):159-72.
  25. Van Der Weijden F, Slot DE. Oral hygiene in the prevention of periodontal diseases: the evidence. Periodontol 2000. 2011;55(1):104-23.
  26. Teughels W, Feres M, Oud V, Martín C, Matesanz P, Herrera D. Adjunctive effect of systemic antimicrobials in periodontitis therapy: A systematic review and meta-analysis. J Clin Periodontol. 2020;47(22):257-81.
  27. Gómez-Sandoval JR, Robles-Cervantes JA, Hernández-González SO, Espinel-Bermudez MC, et al. Efficacy of clindamycin compared with amoxicillin-metronidazole after a 7-day regimen in the treatment of periodontitis in patients with diabetes: a randomized clinical trial. BMJ Open Diabetes Res Care. 2020;8(1):10-13.
  28. McGowan K, Troy. Optimal dose and duration of amoxicillin-plus-metronidazole as an adjunct to non-surgical periodontal therapy: A systematic review and meta-analysis of randomized, placebo-controlled trials. J Clin Periodontol. 2018;45(1):56-67.
  29. Mirzaeei S, Mansurian M, Asare-Addo K, Nokhodchi A. Metronidazole- and Amoxicillin-Loaded PLGA and PCL Nanofibers as Potential Drug Delivery Systems for the Treatment of Periodontitis: In Vitro and In Vivo Evaluations. Biomedicines. 2021;9(8):975.
  30. Amato M, Santonocito S, Polizzi A, Tartaglia GM, Ronsivalle V, Viglianisi G, et al. Local Delivery and Controlled Release Drugs Systems: A New Approach for the Clinical Treatment of Periodontitis Therapy. Pharmaceutics. 2023;15(4):1312.
  31. Benatti BB, Neto JBC, Casati MZ, Sallum EA, Sallum AW, Nociti Jr FH. Periodontal healing may be affected by aging: a histologic study in rats. J Periodontal Res. 2006;41(4):329-33.
  32. Xuan W, Hong-cheng J, Yan-min F, Li-hua H. Chitosan-ascorbate for periodontal tissue healing and regeneration in a rat periodontitis model an effectiveness validation. Chin J Tissue Eng Res. 2010;14(12):2270.
  33. Muzzarelli R, Biagini G, Pugnaloni A, Filippini O, Baldassarre V, Castaldini C, et al. Reconstruction of parodontal tissue with chitosan. Biomaterials. 1989;10(9):598-603.
  34. Faveri M, Retamal-Valdes B, Mestnik MJ, de Figueiredo LC, Barão VAR, Souza JGS, et al. Microbiological effects of amoxicillin plus metronidazole in the treatment of young patients with Stages III and IV periodontitis: A secondary analysis from a 1-year double-blinded placebo-controlled randomized clinical trial. J Periodontol. 2023;94(4):498-508.
  35. Birk SE, Boisen A, Nielsen LH. Polymeric nano- and microparticulate drug delivery systems for treatment of biofilms. Adv Drug Deliv Rev. 2021;17(4):30-52.
  36. Husain MSB, Gupta A, Alashwal BY, Sharma S. Synthesis of PVA/PVP based hydrogel for biomedical applications: a review. Energy Sources, Part A: Recovery, Utilization, and Environmental Effects. Taylor & Francis; 2018;40(20):2388-93.
  37. Poy SY, Bashir S, Omar FS, Saidi NM, Farhana NK, Sundararajan V, et al. Poly (1-vinylpyrrolidone-co-vinyl acetate) (PVP-co-VAc) based gel polymer electrolytes for electric double layer capacitors (EDLC). J Polym Res. 2020;27(3):50.
  38. Kassab H, Vartanian L, Jabir S. Development and physical characterization of a periodontal bioadhesive gel of gatifloxacin. Int J Appl Pharm. 2017;9(3):34.
  39. Ong S-Y, Wu J, Moochhala SM, Tan M-H, Lu J. Development of a chitosan-based wound dressing with improved hemostatic and antimicrobial properties. Biomaterials. 2008;29(32):4323-32.
  40. Ikinci G, Senel S, Akincibay H, Kaş S, Erciş S, Wilson CG, et al. Effect of chitosan on a periodontal pathogen Porphyromonas gingivalis. Int J Pharm. 2002;235(1-2):121-7.
  41. Sah AK, Dewangan M, Suresh PK. Potential of chitosan-based carrier for periodontal drug delivery. Colloids Surf B Biointerfaces. 2019;178(1):185-98.
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