Generic placeholder image

Drug Delivery Letters


ISSN (Print): 2210-3031
ISSN (Online): 2210-304X

Research Article

Metronidazole Loaded Polycaprolactone-Carbopol Blends Based Biodegradable Intrapocket Dental Film for Local Treatment of Periodontitis

Author(s): Nitin Dhedage, Gayasuddin Khan, Gufran Ajmal, Manish Kumar, Abhishek Jha and Brahmeshwar Mishra*

Volume 11 , Issue 1 , 2021

Published on: 10 September, 2020

Page: [34 - 43] Pages: 10

DOI: 10.2174/2210303110999200910104334

Price: $65


Objective: The goal of this research was to optimize and evaluate an intrapocket dental film, composed of polycaprolactone and carbopol blends for the management of periodontitis.

Methods: The intrapocket dental film was prepared using a modified solvent casting method, followed by characterization, in-vitro release, in-vitro antimicrobial activity, and in-vivo efficacy on the periodontitis animal model.

Result: Prepared films were consistent in thickness (2.10±0.56 to 2.50±0.39 mm) and weight (35.23±0.37 to 39.45±0.45 mg) with drug entrapment of up to 87.63±1.98 percent. The concentration of carbopol is observed to have a direct relationship with the thickness, film weight, and swelling factor of the prepared dental film. The film has a surface pH close to gingival crevicular fluid pH and is therefore appropriate for the application. The developed film exhibited a biphasic drug release profile with an initial burst release followed by a continuous release for more than 11 days. Drug release kinetic study supports the release of the drug by a diffusion-based process, as best explained by the Korsmeyer Peppas kinetics (R2 =0.9635). in vitro antimicrobial activity was also in accordance with drug release, with a high initial zone of inhibition (ZOI) (49.32±0.156mm), followed by 14.28±0.080 mm ZOI on the 11th day. The in vivo study showed that the prepared film was able to prevent periodontal ligament degeneration, as observed in the periodontitis experiment animal model.

Conclusion: The prepared intrapocket dental film based on caprolactone and carbopol can be used as a novel local drug delivery system for the management of periodontitis.

Keywords: Dental film, biodegradable, Metronidazole, periodontitis, local drug delivery, antibacterial activity.

Graphical Abstract
Park, D.; Kim, M.; Choi, J.W.; Baek, J.H.; Lee, S.H.; Baek, K. Antimicrobial photodynamic therapy efficacy against specific pathogenic periodontitis bacterial species. Photodiagn. Photodyn. Ther., 2020, 30, 101688.
[] [PMID: 32087294]
Shifrovitch, Y.; Binderman, I.; Bahar, H.; Berdicevsky, I.; Zilberman, M. Metronidazole-loaded bioabsorbable films as local antibacterial treatment of infected periodontal pockets. J. Periodontol., 2009, 80(2), 330-337.
[] [PMID: 19186975]
Budai-Szűcs, M.; Léber, A.; Cui, L.; Józó, M.; Vályi, P.; Burián, K.; Kirschweng, B.; Csányi, E.; Pukánszky, B. Electrospun PLA fibers containing metronidazole for periodontal disease. Drug Des. Devel. Ther., 2020, 14, 233-242.
[] [PMID: 32021107]
Ghavami-Lahiji, M.; Shafiei, F.; Najafi, F.; Erfan, M. Drug-loaded polymeric films as a promising tool for the treatment of periodontitis. J. Drug Deliv. Sci. Technol., 2019, 52, 122-129.
Hunter, M.C.; Pozhitkov, A.E.; Noble, P.A. Microbial signatures of oral dysbiosis, periodontitis and edentulism revealed by Gene Meter methodology. J. Microbiol. Methods, 2016, 131, 85-101.
[] [PMID: 27717873]
Rajeshwari, H.R.; Dhamecha, D.; Jagwani, S.; Rao, M.; Jadhav, K.; Shaikh, S.; Puzhankara, L.; Jalalpure, S. Local drug delivery systems in the management of periodontitis: A scientific review J Controlled Release, 2019, 307, 393-409.
Hiyoshi, T.; Domon, H.; Maekawa, T.; Yonezawa, D.; Kunitomo, E.; Tabeta, K.; Terao, Y. Protective effect of hinokitiol against periodontal bone loss in ligature-induced experimental periodontitis in mice. Arch. Oral Biol., 2020, 112, 104679.
[] [PMID: 32062102]
Ahuja, A.; Ali, J.; Rahman, S. Biodegradable periodontal intrapocket device containing metronidazole and amoxycillin: Formulation and characterisation. Die Pharmazie-An Int. J. Pharm. Sci., 2006, 61(1), 25-29.
[PMID: 16307453]
Bansal, M.; Mittal, N.; Yadav, S.K.; Khan, G.; Gupta, P.; Mishra, B.; Nath, G. Periodontal thermoresponsive, mucoadhesive dual antimicrobial loaded in-situ gel for the treatment of periodontal disease: Preparation, in-vitro characterization and antimicrobial study. J. Oral Biol. Craniofac. Res., 2018, 8(2), 126-133.
[] [PMID: 29892535]
Reise, M.; Wyrwa, R.; Müller, U.; Zylinski, M.; Völpel, A.; Schnabelrauch, M.; Berg, A.; Jandt, K.D.; Watts, D.C.; Sigusch, B.W. Release of metronidazole from electrospun poly(L-lactide-co-D/L-lactide) fibers for local periodontitis treatment. Dent. Mater., 2012, 28(2), 179-188.
[] [PMID: 22226009]
Zamani, M.; Morshed, M.; Varshosaz, J.; Jannesari, M. Controlled release of metronidazole benzoate from poly ε-caprolactone electrospun nanofibers for periodontal diseases. Eur. J. Pharm. Biopharm., 2010, 75(2), 179-185.
[] [PMID: 20144711]
Léber, A.; Budai-Szűcs, M.; Urbán, E.; Vályi, P.; Gácsi, A.; Berkó, S.; Kovács, A.; Csányi, E. Combination of zinc hyaluronate and metronidazole in a lipid-based drug delivery system for the treatment of periodontitis. Pharmaceutics, 2019, 11(3), 142.
[] [PMID: 30934537]
Gad, H.A.; Kamel, A.O.; Ezzat, O.M.; El Dessouky, H.F.; Sammour, O.A. Doxycycline hydrochloride-metronidazole solid lipid microparticles gels for treatment of periodontitis: Development, in-vitro and in-vivo clinical evaluation. Expert Opin. Drug Deliv., 2017, 14(11), 1241-1251.
[] [PMID: 28485988]
Pichayakorn, W.; Boonme, P. Evaluation of cross-linked chitosan microparticles containing metronidazole for periodontitis treatment. Mater. Sci. Eng. C, 2013, 33(3), 1197-1202.
[] [PMID: 23827560]
Ahuja, A.; Rahman, S.; Ali, J.; Chaudhry, R. Effect of dental films containing amoxycillin and metronidazole on periodontal pathogens: Microbiological response. Pharmazie, 2003, 58(10), 716-720.
[PMID: 14609283]
Boroujeni, A.A.; Ardakani, M.T.; Houshmand, B.; Moscowchi, A. Designing a novel chitosan-based periofilm containing metronidazole–ciprofloxacin. SN Appl Sci., 2020, 2(4), 1-8.
Nagaraju, R.; Udupa, N.; Mathew, J.; Varma, B.R. Clinical efficacy of biodegradable dental implants of tinidazole in periodontitis. Indian J. Physiol. Pharmacol., 1999, 43(1), 125-128.
[PMID: 27093751]
Kyun, K.D.; Yun, K.S.; Young, J.S.; Pyoung, C.C.; Heui, S.S. Development of minocycline containing polycaprolactone film as a local drug delivery. Taehan Chikkwa Uisa Hyophoe Chi, 1990, 28(3), 279-290.
[PMID: 2133344]
Nair, A.B.; Kumria, R.; Harsha, S.; Attimarad, M.; Al-Dhubiab, B.E.; Alhaider, I.A. In vitro techniques to evaluate buccal films. J. Control. Release, 2013, 166(1), 10-21.
[] [PMID: 23219961]
Sridevi, S.; JayachandraBabu, R.; Mittal, N.; Sampath Kumar, D.; Pandit, JK. Development and evaluation of acrylic strips of metronidazole for the therapy of periondotal disease. Dev Eval Acrylic Strips Metronidazole Ther Periondotal Dis., 1995, 50(2), 153-154.
Costa, P.; Sousa Lobo, J.M. Modeling and comparison of dissolution profiles. Eur. J. Pharm. Sci., 2001, 13(2), 123-133.
[] [PMID: 11297896]
Taubman, M.A.; Yoshie, H.; Wetherell, J.R., Jr; Ebersole, J.L.; Smith, D.J. Immune response and periodontal bone loss in germfree rats immunized and infected with Actinobacillus actinomycetemcomitans. J. Periodontal Res., 1983, 18(4), 393-401.
[] [PMID: 6227724]
Evans, R.T.; Klausen, B.; Ramamurthy, N.S.; Golub, L.M.; Sfintescu, C.; Genco, R.J. Periodontopathic potential of two strains of Porphyromonas gingivalis in gnotobiotic rats. Arch. Oral Biol., 1992, 37(10), 813-819.
[] [PMID: 1359858]
Abe, T.; Hajishengallis, G. Optimization of the ligature-induced periodontitis model in mice. J. Immunol. Methods, 2013, 394(1-2), 49-54.
[] [PMID: 23672778]
Xu, Y.; Wei, W. A comparative study of systemic subantimicrobial and topical treatment of minocycline in experimental periodontitis of rats. Arch. Oral Biol., 2006, 51(9), 794-803.
[] [PMID: 16712777]
Botelho, M.A.; Martins, J.G.; Ruela, R.S.; Queiroz, D.B.; Ruela, W.S. Nanotechnology in ligature-induced periodontitis: Protective effect of a doxycycline gel with nanoparticules. J. Appl. Oral Sci., 2010, 18(4), 335-342.
[] [PMID: 20835566]
Junmahasathien, T.; Panraksa, P.; Protiarn, P.; Hormdee, D.; Noisombut, R.; Kantrong, N.; Jantrawut, P. Preparation and evaluation of metronidazole-loaded pectin films for potentially targeting a microbial infection associated with periodontal disease. Polymers (Basel), 2018, 10(9), 1021.
[] [PMID: 30960947]
Semalty, A.; Semalty, M.; Nautiyal, U. Formulation and evaluation of mucoadhesive buccal films of enalapril maleate. Indian J. Pharm. Sci., 2010, 72(5), 571-575.
[] [PMID: 21694987]
Agarwal, R.K.; Robinson, D.H.; Maze, G.I.; Reinhardt, R.A. Development and characterization of tetracycline-poly(lactide/glycolide) films for the treatment of periodontitis. J. Control. Release, 1993, 23(2), 137-146.
Braceras, I.; De Maeztu, M.A.; Alava, J.I.; Gay-Escoda, C. In vivo low-density bone apposition on different implant surface materials. Int. J. Oral Maxillofac. Surg., 2009, 38(3), 274-278.
[] [PMID: 19200692]
Xie, R.; Kuijpers-Jagtman, A.M.; Maltha, J.C. Inflammatory responses in two commonly used rat models for experimental tooth movement: Comparison with ligature-induced periodontitis. Arch. Oral Biol., 2011, 56(2), 159-167.
[] [PMID: 20947064]
Kurtiş, B.; Ünsal, B.; Çetiner, D.; Gültekin, E.; Özcan, G.; Çelebi, N.; Ocak, O. Effect of polylactide/glycolide (PLGA) membranes loaded with metronidazole on periodontal regeneration following guided tissue regeneration in dogs. J. Periodontol., 2002, 73(7), 694-700.
[] [PMID: 12146527]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy