Login Register Cart 0
Generic placeholder image

Current Drug Therapy

Editor-in-Chief

ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Assessment of Effect of Intra-pocket Delivery of Metronidazole Loaded NTrimethyl Quaternary Ammonium Chitosan Nanoparticles in Treatment of Periodontal Disease

Author(s): Kritika Garg* and Pravin Tirgar

Volume 18, Issue 1, 2023

Published on: 05 October, 2022

Page: [49 - 67] Pages: 19

DOI: 10.2174/1574885517666220914095657

Price: $65

Abstract

Background: Conventional drugs like metronidazole for periodontitis have shown several drawbacks. Based on in-vitro and acute toxicity studies on metronidazole-loaded n-trimethyl quaternary ammonium chitosan nanoparticles (NTMET NPs), animal studies were carried out to prove their enhanced activities against periodontitis.

Objectives: This study aimed to assess the effect of nanoparticles through an intra-pocket drug delivery concerning body weight, food consumption, clinical signs, gingival index, tooth mobility, inflammatory changes in periodontal tissues, and serum analysis, leading to gingival damage, connective tissues, and alveolar bone resorption.

Methods: A P. gingivalis and ligature-induced periodontitis model was used to evaluate the effect of the drug on rats.

Results: Periodontitis was successfully induced by using P. gingivalis and ligature in rats. It reflected elevated gingival index, tooth mobility, inflammatory changes in tissues, IL-6, TNF- α, and IL -1β compared to the control group and NTMET NPs treated groups. It was also observed that the damage caused to gingival tissues and resorption of alveolar bone was improved by using NTMET NPs.

Conclusion: Based on present findings, we can conclude that NTMET NPs at a dose of 1.8 and 3.6 mg/ml had significant action on periodontal tissues and were able to reverse the effect of P. gingivalis as well as gingival damage and tooth mobility in rats at an administered dose, which was comparable to the IC50 value of a drug. The findings of the current study provide preclinical scientific data to support their clinical use for periodontitis via an intra-pocket drug delivery route.

Keywords: Porphyromonas gingivalis and ligature induced, periodontal disease, enhanced treatment, n-trimethyl quaternary ammonium chitosan derivative, nanotechnology, intra-pocket drug delivery.

« Previous Next »
Graphical Abstract

[1]
Socransky SS, Haffajee AD. The bacterial etiology of destructive periodontal disease: Current concepts. J Periodontol 1992; 63(4s): 322-31.
[http://dx.doi.org/10.1902/jop.1992.63.4s.322]
[2]
Socransky SS. Microbiology of periodontal disease - present status and future considerations. J Periodontol 1977; 48(9): 497-504.
[http://dx.doi.org/10.1902/jop.1977.48.9.497] [PMID: 333085]
[3]
Choi JI, Nakagawa T, Yamada S, Takazoe I, Okuda K. Clinical, microbiological and immunological studies on recurrent periodontal disease. J Clin Periodontol 1990; 17(7 Pt 1): 426-34.
[PMID: 2201704]
[4]
Page RC, Offenbacher S, Schroeder H, Seymour GJ, Kornman KS. Advances in the pathogenesis of periodontitis: Summary of developments, clinical implications and future directions. Periodontol 2000 1997; 14(1): 216-48.
[http://dx.doi.org/10.1111/j.1600-0757.1997.tb00199.x] [PMID: 9567973]
[5]
Salvi G, Lawrence HP, Offenbacher S, Beck JD. Influence of risk factors on the pathogenesis of periodontitis. Periodontol 2000 1997; 14(1): 173-201.
[http://dx.doi.org/10.1111/j.1600-0757.1997.tb00197.x] [PMID: 9567971]
[6]
Hart TC, Kornman KS. Genetic factors in the pathogenesis of periodontitis. Periodontol 2000 1997; 14(1): 202-15.
[http://dx.doi.org/10.1111/j.1600-0757.1997.tb00198.x] [PMID: 9567972]
[7]
Kornman KS, Crane A, Wang HY, et al. The interleukin-1 genotype as a severity factor in adult periodontal disease. J Clin Periodontol 1997; 24(1): 72-7.
[http://dx.doi.org/10.1111/j.1600-051X.1997.tb01187.x] [PMID: 9049801]
[8]
Garg K, Tirgar P. Local delivery of metronidazole loaded N-trimethyl quaternary ammonium chitosan nanoparticles for periodontitis treatment. Curr Drug Ther 2022; 17: 17.
[http://dx.doi.org/10.2174/1574885517666220331145439]
[9]
Lee HJ, Lee DR, Choi BK, Yang SH. Antiperiodontitis effects of Magnolia biondii extract on ligature-induced periodontitis in rats. Nutrients 2019; 11(4): 934.
[http://dx.doi.org/10.3390/nu11040934] [PMID: 31027223]
[10]
Jain A, Batista EL Jr, Serhan C, Stahl GL, Van Dyke TE. Role for periodontitis in the progression of lipid deposition in an animal model. Infect Immun 2003; 71(10): 6012-8.
[http://dx.doi.org/10.1128/IAI.71.10.6012-6018.2003] [PMID: 14500522]
[11]
Hasturk H, Jones VL, Andry C, Kantarci A. 1-Tetradecanol complex reduces progression of Porphyromonas gingivalis-induced experimental periodontitis in rabbits. J Periodontol 2007; 78(5): 924-32.
[http://dx.doi.org/10.1902/jop.2007.060293] [PMID: 17470028]
[12]
de Molon RS, de Avila ED, Cirelli JA. Host responses induced by different animal models of periodontal disease: A literature review. J Investig Clin Dent 2013; 4(4): 211-8.
[http://dx.doi.org/10.1111/jicd.12018] [PMID: 23188588]
[13]
Dharmawati IA, Manuaba IBP, Thahir H, et al. Pocket measurement methods in wistar rats periodontitis induced by bacteria and the installation of silk ligature: An experimental studies. Int J App Pharm 2019; 11(4): 71-4.
[14]
Lu H, Xu M, Wang F, et al. Chronic stress accelerates ligature-induced periodontitis by suppressing glucocorticoid receptor-α signaling. Exp Mol Med 2016; 48(3): e223.
[http://dx.doi.org/10.1038/emm.2015.127] [PMID: 27012709]
[15]
AlJehani YA. Risk factors of periodontal disease: Review of the literature. Int J Dent 2014; 2014: 1-9.
[http://dx.doi.org/10.1155/2014/182513] [PMID: 24963294]
[16]
Li H, Peng L. Antimicrobial and antioxidant surface modification of cellulose fibers using layer-by-layer deposition of chitosan and lignosulfonates. Carbohydr Polym 2015; 124: 35-42.
[http://dx.doi.org/10.1016/j.carbpol.2015.01.071] [PMID: 25839791]
[17]
Sepúlveda RV, Reis ECC, Valente FL, Brezinski DG, Borges APB. Evaluation of a model for induction of periodontal disease in dogs. Pesqui Vet Bras 2014; 34(6): 562-8.
[http://dx.doi.org/10.1590/S0100-736X2014000600010]
[18]
Ahmed MG, Harish NM, Charyulu RN, Prabhu P. Formulation of chitosan-based ciprofloxacin and diclofenac film for periodontitis therapy. Trop J Pharm Res 2009; 8(1): 33-41.
[http://dx.doi.org/10.4314/tjpr.v8i1.14710]
[19]
Ahmed M, Charyulu RN, Harish NM, Prabhu P. Formulation and in-vitro evaluation of Chitosan films containing tetracycline for the treatment of periodontitis. Asian J Pharm 2009; 3(2): 113-9.
[http://dx.doi.org/10.4103/0973-8398.55048]
[20]
Ahuja A, Ali J, Rahman S. Biodegradable periodontal intrapocket device containing metronidazole and amoxycillin: Formulation and characterisation. Pharmazie 2006; 61(1): 25-9.
[PMID: 16454202]
[21]
Slots J, Rams TE. Antibiotics in periodontal therapy: Advantages and disadvantages. J Clin Periodontol 1990; 17(7 (Pt 2)): 479-93.
[http://dx.doi.org/10.1111/j.1365-2710.1992.tb01220.x] [PMID: 2202744]
[22]
Pitcher GR, Newman HN, Strahan JD. Access to subgingival plaque by disclosing agents using mouthrinsing and direct irrigation. J Clin Periodontol 1980; 7(4): 300-8.
[http://dx.doi.org/10.1111/j.1600-051X.1980.tb01972.x] [PMID: 6936408]
[23]
Gates KA, Grad H, Birek P, Lee PI. A new bioerodible polymer insert for the controlled release of metronidazole. Pharm Res 1994; 11(11): 1605-9.
[http://dx.doi.org/10.1023/A:1018913921956] [PMID: 7870678]
[24]
Sudarshan NR, Hoover DG, Knorr D. Antibacterial action of chitosan. Food Biotechnol 1992; 6(3): 257-72.
[http://dx.doi.org/10.1080/08905439209549838]
[25]
Zheng LY, Zhu JF. Study on antimicrobial activity of chitosan with different molecular weights. Carbohydr Polym 2003; 54(4): 527-30.
[http://dx.doi.org/10.1016/j.carbpol.2003.07.009]
[26]
Rhoades J, Roller S. Antimicrobial actions of degraded and native chitosan against spoilage organisms in laboratory media and foods. Appl Environ Microbiol 2000; 66(1): 80-6.
[http://dx.doi.org/10.1128/AEM.66.1.80-86.2000] [PMID: 10618206]
[27]
Younes I, Sellimi S, Rinaudo M, Jellouli K, Nasri M. Influence of acetylation degree and molecular weight of homogeneous chitosans on antibacterial and antifungal activities. Int J Food Microbiol 2014; 185: 57-63.
[http://dx.doi.org/10.1016/j.ijfoodmicro.2014.04.029] [PMID: 24929684]
[28]
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): E184-94.
[http://dx.doi.org/10.1208/pt0803075] [PMID: 17915825]
[29]
Oz HS, Puleo DA. Animal models for periodontal disease. J Biomed Biotechnol 2011; 2011: 1-8.
[http://dx.doi.org/10.1155/2011/754857] [PMID: 21331345]
[30]
Kantarci A, Hasturk H, Van Dyke TE. Animal models for periodontal regeneration and peri-implant responses. Periodontol 2000 2015; 68(1): 66-82.
[http://dx.doi.org/10.1111/prd.12052] [PMID: 25867980]
[31]
Graves DT, Kang J, Andriankaja O, Wada K, Rossa C Jr. Animal models to study host-bacteria interactions involved in periodontitis. Front Oral Biol 2012; 15: 117-32.
[http://dx.doi.org/10.1159/000329675] [PMID: 22142960]
[32]
Hajishengallis G. Immunomicrobial pathogenesis of periodontitis: Keystones, pathobionts, and host response. Trends Immunol 2014; 35(1): 3-11.
[http://dx.doi.org/10.1016/j.it.2013.09.001] [PMID: 24269668]
[33]
Cai X, Li C, Du G, Cao Z. Protective effects of baicalin on ligature-induced periodontitis in rats. J Periodontal Res 2008; 43(1): 14-21.
[PMID: 18230102]
[34]
Ionel A, Lucaciu O, Moga M, et al. Periodontal disease induced in wistar rats - experimental study. Hum Vet Med Int J Bioflux Soc 2015; 7(2): 90-5.
[35]
Jönsson D, Nebel D, Bratthall G, Nilsson BO. The human periodontal ligament cell: A fibroblast-like cell acting as an immune cell. J Periodontal Res 2011; 46(2): 153-7.
[http://dx.doi.org/10.1111/j.1600-0765.2010.01331.x] [PMID: 21118418]

Rights & Permissions Print Cite
Article Metrics
21
2
© 2024 Bentham Science Publishers | Privacy Policy