Advances in Periodontal Drug Delivery Systems and the Role of Probiotics in Periodontitis Treatment

Pratikshya Mohanty ¹, Kalpita Bhatta ^1*, Itishree Jogamaya Das ²,  Himansu Bhusan Samal ^3*

This review discussed the periodontitis and its prevalence in gum inflammation and bone loss. Local drug delivery systems offer effective treatment, enhancing patient care.

Abstract

Periodontitis is a group of inflammatory diseases which results the destruction of tooth-supporting tissues and affects 20-50% of the global population. Different bacterial enzymes are released into the periodontal pockets as a result of the proliferation of varied microflora, particularly anaerobes, which affect the body's immune response. A key component of treating periodontitis is mounting along with routing. Soluble at the site of infection, nonoperative controlled-release formulations reduce the requirement for systemic dosage by providing an affordable, non-toxic, biocompatible, and long-term therapeutic alternative. To successfully deliver a drug variety, several polymer-based systems can be used, i.e., strips, microparticles, fibers, nanoparticles, films, and nanofibers. This paper reviews the potential benefits and limits of using periodontal pockets as a medication delivery platform to create an appropriate dental localized dose form. The microorganisms called probiotics are present in the human body's alimentary canal and saliva. Recent studies on the usage of these organisms in treating periodontitis have substantially sparked the interest of researchers due to the positive metabolic effects of these organisms. Therefore, more study is needed to understand better how probiotics function physiologically and to manage periodontal disease over the long term.

Keywords: Periodontitis, controlled drug delivery, Microflora, Nanocarriers, Mucoadhesion, Probiotics.

References

Allaker, R. P., & Stephen, A. S. (2017). Use of probiotics and oral health. Current oral health reports, 4, 309-318.

Amato, M., Santonocito, S., Polizzi, A., Tartaglia, G. M., Ronsivalle, V., Viglianisi, G., Isola, G. (2023). Local Delivery and Controlled Release Drugs Systems: A New Approach for the Clinical Treatment of Periodontitis Therapy. Pharmaceutics, 15(4), 1312.

Aoki, T., Hiura, F., Li, A., Yang, N., Takakura-Hino, N., Mukai, S., Jimi, E. (2023). Inhibition of non-canonical NF-κB signaling suppresses periodontal inflammation and bone loss. Frontiers in Immunology, 14, 1179007.

Baba, S., Yamada, Y., Komuro, A., Yotsui, Y., Umeda, M., Shimuzutani, K., Nakamura, S. (2016). Phase I/II trial of autologous bone marrow stem cell transplantation with a three-dimensional woven-fabric scaffold for periodontitis. Stem cells international, 2016.

Bhaskaran Sathyapriya, Swamikannu Bhuminathan, Jayesh S Raghavendra et al., (2021), Assessment of Apprehension Related with Noise in Dental Office Among Children in The Age Group 6-15 Years,  Journal of Angiotherapy, 5(2), 1-12

Bunyaratavej, P., Wang, H. L. (2001). Collagen membranes: a review. Journal of periodontology, 72(2), 215-229.

Carlson-Mann, L. D., Ibbott, C. G., Grieman, R. B. (1996). Ridge augmentation with guided bone regeneration and GTAM case illustrations. Probe (Ottawa, Ont.), 30(6), 232-233.

Chhina, S., Rathore, A. S., Juneja, S. (2015). Alpha-2-Macroglobulin Levels in Gingival Crevicular Fluid Pre-and Post-scaling and Root Planing with Adjunctive Tetracycline Fibers in Chronic Periodontitis: A Randomized Controlled Trial. The Journal of Contemporary Dental Practice, 16(6), 474-478.

Clifford, L. R., Needleman, I. G., & Chan, Y. K. (1999). Comparison of periodontal pocket penetration by conventional and micro ultrasonic inserts. Journal of clinical periodontology, 26(2), 124-130.

Deasy, P. B., Collins, A. E., Maccarthy, D. J., Russell, R. J. (1989). Use of strips containing tetracycline hydrochloride or metronidazole for the treatment of advanced periodontal disease. Journal of pharmacy and pharmacology, 41(10), 694-699.

Deporter, D. A. (1988). Periodontal disease part II: overview of treatment modalities. Canadian Family Physician, 34, 1391.

Dong, W. Y., Körber, M., Esguerra, V. L., Bodmeier, R. (2006). Stability of poly (D, L-lactide-co-glycolide) and leuprolide acetate in in-situ forming drug delivery systems. Journal of controlled release, 115(2), 158-167.

Eastham, J. E., & Seymour, R. A. (2014). Local drug delivery in the management of periodontal diseases part 1: general principles. Dental Update, 41(8), 732-736

Flemmig, T. F., Epp, B., Funkenhauser, Z., Newman, M. G., Kornman, K. S., Haubitz, I., & Klaiber, B. (1995). Adjunctive supragingival irrigation with acetylsalicyclic acid in periodontal supportive therapy. Journal of clinical periodontology, 22(6), 427-433.

Freeman, E. (1988). Periodontal disease part III: chemotherapeutics. Canadian Family Physician, 34, 1395.

Furumoto, H., Nanthirudjanar, T., Kume, T., Izumi, Y., Park, S. B., Kitamura, N., Sugawara, T. (2016). 10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress. Toxicology and applied pharmacology, 296, 1-9.

Gad, H. A., Kamel, A. O., Ezzat, O. M., El Dessouky, H. F., Sammour, O. A. (2017). Doxycycline hydrochloride-metronidazole solid lipid microparticles gels for treatment of periodontitis: Development, in-vitro and in-vivo clinical evaluation. Expert opinion on drug delivery, 14(11), 1241-1251.

Garcia, V. G., Knoll, L. R., Longo, M., Novaes, V. C. N., Assem, N. Z., Ervolino, E., Theodoro, L. H. (2016). Effect of the probiotic Saccharomyces cerevisiae on ligature-induced periodontitis in rats. Journal of periodontal research, 51(1), 26-37.

Giusto, T. (1997). Non-surgical vs. surgical periodontal therapy. New York, USA: SUNY Stonybrook, 1.

Goodson, J. M., Haffajee, A., Socransky, S. S. (1979). Periodontal therapy by local delivery of tetracycline. Journal of Clinical Periodontology, 6(2), 83-92.

Hajishengallis, G., Chavakis, T., Lambris, J. D. (2020). Current understanding of periodontal disease pathogenesis and targets for host-modulation therapy. Periodontology 2000, 84(1), 14-34.

HI, B. (1998). Floss or die: implications for dental professionals. Dent today, 17, 80-82.

Hill, C., Guarner, F., Reid, G., Gibson, G. R., Merenstein, D. J., Pot, B., & Sanders, M. E. (2014). Activity of cecropin P1 and FA-LL-37 against urogenital microflora. Nature Reviews Gastroenterology and Hepatology, 11(8), 506.

Huang, Y. K., & Chang, Y. C. (2022). Oral health: the first step to sustainable development goal 3. Journal of the Formosan Medical Association, 121(7), 1348-1350.

Ince, G., Gürsoy, H., Ipçi, S. D., Cakar, G., Emekli-Alturfan, E., & Yilmaz, S. (2015). Clinical and biochemical evaluation of lozenges containing Lactobacillus reuteri as an adjunct to non-surgical periodontal therapy in chronic periodontitis. Journal of periodontology, 86(6), 746-754.

Invernici, M. M., Furlaneto, F. A., Salvador, S. L., Ouwehand, A. C., Salminen, S., Mantziari, A., Messora, M. R. (2020). Bifidobacterium animalis subsp lactis HN019 presents antimicrobial potential against periodontopathogens and modulates the immunological response of oral mucosa in periodontitis patients. PLoS One, 15(9), e0238425.

Jain, S. K., Sahu, A., & Keservani, R. K. (2023). Oral Drug Delivery System: An Overview on

Joshi, D., Garg, T., Goyal, A. K., Rath, G. (2016). Advanced drug delivery approaches against periodontitis. Drug delivery, 23(2), 363-377.

Kaplish, V., Walia, M. K., Kumar, H. S. (2013). Local drug delivery systems in the treatment of periodontitis: A review. Pharmacophore, 4(2), 39-49.

Khorshidi, S., Solouk, A., Mirzadeh, H., Mazinani, S., Lagaron, J. M., Sharifi, S., Ramakrishna, S. (2016). A review of key challenges of electrospun scaffolds for tissue-engineering applications. Journal of tissue engineering and regenerative medicine, 10(9), 715-738.

Krayer, J. W., Leite, R. S., & Kirkwood, K. L. (2010). Non-surgical chemotherapeutic treatment strategies for the management of periodontal diseases. Dental Clinics, 54(1), 13-33.

Kotb, S. (2023). Overview of Periodontal Disease, Etiology, Pathogenesis, Diagnosis and Treatment Therapy: Systematic Review Article. Etiology, Pathogenesis, Diagnosis and Treatment Therapy: Systematic Review Article.

Lang, N. P., & Räber, K. (1981). Use of oral irrigators as vehicle for the application of antimicrobial agents in chemical plaque control. Journal of Clinical Periodontology, 8(3), 177-188.

Lang, N. P., & Ramseier-Grossmann, K. (1981). Optimal dosage of chlorhexidine digluconate in chemical plaque control when applied by the oral irrigator. Journal of clinical periodontology, 8(3), 189-202.

Liang, J., Peng, X., Zhou, X., Zou, J., Cheng, L. (2020). Emerging applications of drug delivery systems in oral infectious diseases prevention and treatment. Molecules, 25(3), 516.

Liccardo, D., Cannavo, A., Spagnuolo, G., Ferrara, N., Cittadini, A., Rengo, C., Rengo, G. (2019). Periodontal disease: a risk factor for diabetes and cardiovascular disease. International journal of molecular sciences, 20(6), 1414.

Lilly, D. M., & Stillwell, R. H. (1965). Probiotics: growth-promoting factors produced by microorganisms. Science, 147(3659), 747-748.

Minic, I., Pejcic, A., Bradic-Vasic, M. (2022). Effect of the local probiotics in the therapy of periodontitis A randomized prospective study. International Journal of Dental Hygiene, 20(2), 401-407.

Nazir, M., Al-Ansari, A., Al-Khalifa, K., Alhareky, M., Gaffar, B., Almas, K. (2020). Global prevalence of periodontal disease and lack of its surveillance. The Scientific World Journal, 2020.

Nguyen-Thi, T. D., Nguyen-Huynh, B. H., Vo-Hoang, T. T., Nguyen-Thanh, T. (2023). Stem cell therapies for periodontal tissue regeneration: A meta-analysis of clinical trials. Journal of Oral Biology and Craniofacial Research, 13(5), 589-597.

Nguyen, T., Brody, H., Radaic, A., Kapila, Y. (2021). Probiotics for periodontal health—Current molecular findings. Periodontology 2000, 87(1), 254-267.

Ohshima, T., Kojima, Y., & Seneviratne, C. J. (2016). Therapeutic application of synbiotics, a fusion of probiotics and prebiotics, and biogenics as a new concept for oral Candida infections: a mini review. Frontiers in Microbiology, 7, 168868.

Oliver, R. C., Brown, L. J., & Löe, H. (1998). Periodontal diseases in the United States population. Journal of periodontology, 69(2), 269-278.

Oringer, R. J. (2002). Modulation of the host response in periodontal therapy. Journal of periodontology, 73(4), 460-470

Ouchi, T., Nakagawa, T. (2020). Mesenchymal stem cell-based tissue regeneration therapies for periodontitis. Regenerative Therapy, 14, 72-78.

Qasim, S. S. B., Nogueria, L. P., Fawzy, A. S., & Daood, U. (2020). The effect of cross-linking efficiency of drug-loaded novel freeze gelated chitosan templates for periodontal tissue regeneration. AAPS Pharm SciTech, 21, 1-9.

Qi, Y., Yang, J., Chi, Y., Wen, P., Wang, Z., Yu, S., Han, B. (2022). Natural polyphenol self-assembled pH-responsive nanoparticles loaded into reversible hydrogel to inhibit oral bacterial activity. Molecular Biomedicine, 3(1), 28.

Rajababu, P., Harinath, R. S., Satyanarayana, D., & Sunil, K. P. (2009). Nonsurgical periodontal therapy. Indian Journal of Dental Advancements, 1(1), 16-20.

Rajeshwari, H. R., Dhamecha, D., Jagwani, S., Rao, M., Jadhav, K., Shaikh, S., Jalalpure, S. (2019). Local drug delivery systems in the management of periodontitis: A scientific review. Journal of Controlled Release, 307, 393-409.

Riaz, B., Sohn, S. (2023). Neutrophils in Inflammatory Diseases: Unravelling the Impact of Their Derived Molecules and Heterogeneity. Cells, 12(22), 2621.

Ryan, M. E. (2005). Nonsurgical approaches for the treatment of periodontal diseases. Dental Clinics, 49(3), 611-636.

Samal, H. B., Patra, N., Boyeena, L., & Das, I. J. (2021). Novel Periodontal Pocket Drug Delivery Systems for The Treatment of Periodontitis. Indian Drugs, 58(3).

Sheikh, Z., Qureshi, J., Alshahrani, A. M., Nassar, H., Ikeda, Y., Glogauer, M., Ganss, B. (2017). Collagen based barrier membranes for periodontal guided bone regeneration applications. Odontology, 105, 1-12.

Slots, J., & Rams, T. E. (1990). Antibiotics in periodontal therapy: advantages and disadvantages. Journal of clinical periodontology, 17, 479-493

Srinivasan, S., Mahendra, J., Kanakamedala, A., Namasivayam, A. (2020). A Review On Probiotics–A New Paradigm in Periodontal Health. Annals of the Romanian Society for Cell Biology, 483-489.

Sulijaya, B., Yamada-Hara, M., Yokoji-Takeuchi, M., Matsuda-Matsukawa, Y., Yamazaki, K., Matsugishi, A., Yamazaki, K. (2019). Antimicrobial function of the polyunsaturated fatty acid KetoC in an experimental model of periodontitis. Journal of Periodontology, 90(12), 1470-1480.

Visentin, D., Gobin, I., Maglica, Ž. (2023). Periodontal Pathogens and Their Links to Neuroinflammation and Neurodegeneration. Microorganisms, 11(7), 1832.

Wang, B., Wang, J., Shao, J., Kouwer, P. H., Bronkhorst, E. M., Jansen, J. A., Yang, F. (2020). A tunable and injectable local drug delivery system for personalized periodontal application. Journal of Controlled Release, 324, 134-145.

Wei, Y., Deng, Y., Ma, S., Ran, M., Jia, Y., Meng, J., Tang, X. (2021). Local drug delivery systems as therapeutic strategies against periodontitis: A systematic review. Journal of Controlled Release, 333, 269-282.

Wu, L., Chen, W., Li, F., Morrow, B. R., Garcia-Godoy, F., Hong, L. (2018). Sustained release of minocycline from minocycline-calcium-dextran sulfate complex microparticles for periodontitis treatment. Journal of pharmaceutical sciences, 107(12), 3134-3142.

Xu, S., Zhou, Q., Jiang, Z., Wang, Y., Yang, K., Qiu, X., Ji, Q. (2020). The effect of doxycycline-containing chitosan/carboxymethyl chitosan nanoparticles on NLRP3 inflammasome in periodontal disease. Carbohydrate polymers, 237, 116163.

Zhang, Y., Ding, Y., Guo, Q. (2022). Probiotic species in the management of periodontal diseases: An overview. Frontiers in cellular and infection microbiology, 12, 308.