DOI:

10.37988/1811-153X_2022_4_74

Experimental substantiation of the development of the dosage form of lactoferrin with enamel matrix derivatives for use in periodontology

Authors

  • M.S. Podporin 1, PhD in Medical Sciences, researcher at the Molecular biology research Laboratory of the Medico-dental research Institute
    ORCID ID: 0000-0001-6785-0016
  • V.N. Tsarev 1, PhD in Medical Sciences, director of the Medico-dental research Institute
    ORCID ID: 0000-0002-3311-0367
  • E.V. Ippolitov 1, PhD in Medical Sciences, leading researcher at the Molecular biology research Laboratory of the Medico-dental research Institute
    ORCID ID: 0000-0003-1737-0887
  • T.V. Tsareva 1, PhD in Medical Sciences, associate professor of the Microbiology, virology, immunology Department
    ORCID ID: 0000-0001-9571-0520
  • V.V. Vishlenkova 1, 4th year student at the Medical Faculty
    ORCID ID: 0000-0001-6065-1997
  • I.L. Goldman 2, PhD in Medical Sciences, leading researcher
    ORCID ID: 0000-0003-1534-3367
  • E.R. Sadchikova 2, PhD in Chemical Sciences, deputy director
    ORCID ID: 0000-0003-2039-7108
  • 1 Moscow State University of Medicine and Dentistry, 127473, Moscow, Russia
  • 2 Institute of Gene Biology of the Russian Academy of Sciences, 119334, Moscow, Russia

Abstract

When performing reconstructive operations in periodontology, the use of a derivative of the enamel matrix Emdogaine, which stimulates the regeneration of soft tissues well, is promising, but it is not always effective enough against infectious inflammation. Lactoferrin is considered among the possible candidate drugs that have an anti-inflammatory antimicrobial effect. The aim of the study was to experimentally substantiate the antimicrobial action of lactoferrin in combination with enamel matrix derivatives in the formation of a depot of a complex drug. >. To assess the antimicrobial activity of the Emdogaine and lactoferrin complex, programmed automatic cultivation of S. aureus was performed. The results were recorded non-invasively, using the built-in optical density measurement system, in accordance with the key points of culture development in the periodic cultivation system. Statistical processing was carried out by constructing a regression dependence (a second-order parabola), with an estimate of the Fisher criterion and the Pearson correlation coefficient. Results and discussion. When cultivating S. aureus with Emdogaine, there was no statistically significant difference in the change in optical density relative to the control sample, compared with both lactoferrin and its combination with osteoplastic material, which demonstrated a pronounced antibacterial effect. The result obtained was statistically reliable. >. The use of lactoferrin in combination with the osteoplastic material Emdogaine leads to a new quality of the complex — prolonged bacteriostatic action against the studied microbial populations and can be recommended for the development of a dosage form with regeneration stimulating and antimicrobial properties.

Key words:

lactoferrin, bioreactor, bone regeneration, periodontitis, enamel matrix, protein

For Citation

[1]
Podporin M.S., Tsarev V.N., Ippolitov E.V., Tsareva T.V., Vishlenkova V.V., Goldman I.L., Sadchikova E.R. Experimental substantiation of the development of the dosage form of lactoferrin with enamel matrix derivatives for use in periodontology. Clinical Dentistry (Russia).  2022; 25 (4): 74—80. DOI: 10.37988/1811-153X_2022_4_74

References

  1. Kao R.T., Nares S., Reynolds M.A. Periodontal regeneration intrabony defects: a systematic review from the AAP Regeneration Workshop. J Periodontol. 2015; 86 (2 Suppl): S77—104. PMID: 25216204
  2. Needleman I.G., Worthington H.V., Giedrys‐Leeper E., Tucker R.J. Guided tissue regeneration for periodontal infra‐bony defects. Cochrane Database of Systematic Reviews. 2006, Issue 2. PMID: 16625546
  3. A.P. Parakhonsky, Perova N.Y. The role of cytokines in the pathogenesis of periodontitis. Natural-humanitarian studies. 2015; 1 (7): 75—81 (In Russ.). eLIBRARY ID: 23024166
  4. Balmasova I.P., Tsarev V.N., Yanushevich O.O., Maev I.V., Mkrtumyan M.A., Arutyunov S.D. Microecology of the periodontium. The relationship of local and systemic effects. Moscow: Practical medicine, 2021. P. 264. (In Russ.).
  5. Tan O.L., Safii S.H., Razali M. Commercial local pharmacotherapeutics and adjunctive agents for nonsurgical treatment of periodontitis: A contemporary review of clinical efficacies and challenges. Antibiotics (Basel). 2019; 9 (1): 10. PMID: 31905889
  6. Rojas M.A., Marini L., Pilloni A., Sahrmann P. Early wound healing outcomes after regenerative periodontal surgery with enamel matrix derivatives or guided tissue regeneration: a systematic review. BMC Oral Health. 2019; 19 (1): 76. PMID: 31064353
  7. Menicanin D., Hynes K., Han J., Gronthos S., Bartold P.M. Cementum and Periodontal Ligament Regeneration. Adv Exp Med Biol. 2015; 881: 207—36. PMID: 26545752
  8. Xu X., Chen X., Li J. Natural protein bioinspired materials for regeneration of hard tissues. J Mater Chem B. 2020; 8 (11): 2199—2215. PMID: 32091067
  9. Elzoghby A.O., Abdelmoneem M.A., Hassanin I.A., Abd Elwakil M.M., Elnaggar M.A., Mokhtar S., Fang J.Y., Elkhodairy K.A. Lactoferrin, a multi-functional glycoprotein: Active therapeutic, drug nanocarrier & targeting ligand. Biomaterials. 2020; 263: 120355. PMID: 32932142
  10. Rosa L., Lepanto M.S., Cutone A., Ianiro G., Pernarella S., Sangermano R., Musci G., Ottolenghi L., Valenti P. Lactoferrin and oral pathologies: a therapeutic treatment. Biochem Cell Biol. 2021; 99 (1): 81—90. PMID: 32213143
  11. Hwang S.A., Wilk K.M., Bangale Y.A., Kruzel M.L., Actor J.K. Lactoferrin modulation of IL-12 and IL-10 response from activated murine leukocytes. Med Microbiol Immunol. 2007; 196 (3): 171—80. PMID: 17377816
  12. Kuhara T., Yamauchi K., Tamura Y., Okamura H. Oral administration of lactoferrin increases NK cell activity in mice via increased production of IL-18 and type I IFN in the small intestine. J Interferon Cytokine Res. 2006; 26 (7): 489—99. PMID: 16800788
  13. Tsarev V.N., Atrushkevich V.G., Ippolitov E.V., Podporin M.S. Comparative analysis of periodontal antiseptic antimicrobial activity using the automated control of microbial growth in real-time. Parodontologiya. 2017; 1 (82): 4—10 (In Russ.). eLIBRARY ID: 29233663
  14. Ushakov R.V., Tsarev V.N. Antimicrobial therapy in dentistry. Principles and algorithms. Moscow: Practical medicine, 2019. 240 p. (In Russ.).
  15. Tsarev V.N., Drobyshev A.Y., Ippolitov E.V., Labazanov A.A., Podporin M.S., Tsareva T.V., Trefilova Y.A. Combined antibacterial chemotherapy odontogenic infection-why Ciprofloxacin with Tinidazole?. Clinical Dentistry (Russia). 2020; 1 (93): 18—24 (In Russ.). eLIBRARY ID: 42846259
  16. Wang Y.C., Ma H.D., Yin X.Y., Wang Y.H., Liu Q.Z., Yang J.B., Shi Q.H., Sun B., Gershwin M.E., Lian Z.X. Forkhead box O1 regulates macrophage polarization following Staphylococcus aureus infection: Experimental murine data and review of the literature. Clin Rev Allergy Immunol. 2016; 51 (3): 353—369. PMID: 26924010
  17. Enigk K., Jentsch H., Rodloff A.C., Eschrich K., Stingu C.S. Activity of five antimicrobial peptides against periodontal as well as non-periodontal pathogenic strains. J Oral Microbiol. 2020; 12 (1): 1829405. PMID: 33133417
  18. Eberhard J., Jepsen S., Jervøe-Storm P.M., Needleman I., Worthington H.V. Full-mouth treatment modalities (within 24 hours) for chronic periodontitis in adults. Cochrane Database Syst Rev. 2015; 2015 (4): CD004622. PMID: 25884249
  19. Karav S., German J.B., Rouquié C., Le Parc A., Barile D. Studying Lactoferrin N-Glycosylation. Int J Mol Sci. 2017; 18 (4): 10. PMID: 28425960
  20. Spadaro M., Caorsi C., Ceruti P., Varadhachary A., Forni G., Pericle F., Giovarelli M. Lactoferrin, a major defense protein of innate immunity, is a novel maturation factor for human dendritic cells. FASEB J. 2008; 22 (8): 2747—57. PMID: 18364398
  21. Esposito M., Grusovin M.G., Papanikolaou N., Coulthard P., Worthington H.V. Enamel matrix derivative (Emdogain (R)) for periodontal tissue regeneration in intrabony defects. Cochrane Database Syst Rev. 2009; 2009 (4): CD003875. PMID: 19821315
  22. Wyganowska-Świątkowska M., Szkaradkiewicz A.K., Karpiński T.M., Marcinkowski J.T. The evaluation of enamel matrix derivative on subgingival microbial environment in non-surgical periodontal therapy. Ann Agric Environ Med. 2013; 20 (3): 431—5. PMID: 24069844
  23. Najeeb S., Khurshid Z., Sohail Zafar M., Zohaib S., Siddiqui F. Efficacy of enamel matrix derivative in vital pulp therapy: A review of literature. Iran Endod J. 2017; 12 (3): 269—275. PMID: 28808449
  24. Walter C., Jawor P., Bernimoulin J.P., Hägewald S. Moderate effect of enamel matrix derivative (Emdogain Gel) on Porphyromonas gingivalis growth in vitro. Arch Oral Biol. 2006; 51 (3): 171—6. PMID: 16137640

Received

November 7, 2022

Accepted

November 15, 2022

Published on

December 21, 2022