Treatment modalities and evaluation models for periodontitis

Mohammad Tariq, Zeenat Iqbal, Javed Ali, Sanjula Baboota, Sushama Talegaonkar, Zulfiqar Ahmad, Jasjeet K Sahni, Mohammad Tariq, Zeenat Iqbal, Javed Ali, Sanjula Baboota, Sushama Talegaonkar, Zulfiqar Ahmad, Jasjeet K Sahni

Abstract

Periodontitis is the most common localized dental inflammatory disease related with several pathological conditions like inflammation of gums (gingivitis), degeneration of periodontal ligament, dental cementum and alveolar bone loss. In this perspective, the various preventive and treatment modalities, including oral hygiene, gingival irrigations, mechanical instrumentation, full mouth disinfection, host modulation and antimicrobial therapy, which are used either as adjunctive treatments or as stand-alone therapies in the non-surgical management of periodontal infections, have been discussed. Intra-pocket, sustained release systems have emerged as a novel paradigm for the future research. In this article, special consideration is given to different locally delivered anti-microbial and anti inflammatory medications which are either commercially available or are currently under consideration for Food and Drug Administration (FDA) approval. The various in vitro dissolution models and microbiological strain investigated to impersonate the infected and inflamed periodontal cavity and to predict the in vivo performance of treatment modalities have also been thrashed out. Animal models that have been employed to explore the pathology at the different stages of periodontitis and to evaluate its treatment modalities are enlightened in this proposed review.

Keywords: Chemotherapeutic agents; intra-pocket devices; mechanical therapies; oral hygiene.

Conflict of interest statement

Conflict of Interest: None declared.

Figures

Figure 1
Figure 1
Anatomy of healthy, infected and diseased tooth
Figure 2
Figure 2
Progression of disease and intervention therapies

References

    1. Haffajee AD, Socransky SS. Attachment level changes in destructive periodontal diseases. J Clin Periodontol. 1986;13:461–75.
    1. Jain N, Jain GK, Javed S, Iqbal Z, Talegaonkar S, Ahmad FJ, et al. Recent approaches for the treatment of periodontitis. Drug Dis Today. 2008;13:932–43.
    1. Ryan ME. Nonsurgical approaches for the treatment of periodontal diseases. Dent Clinics North Am. 2005;49:611–36.
    1. Socransky SS. The relationship of bacteria to the etiology of periodontal disease. J Dent Res. 1970;49:203–22.
    1. Howell TH, Williams RC. Nonsteroidal anti-inflammatory drugs as inhibitors of periodontal disease progression. Crit Rev Oral Biol Med. 1993;4:177–96.
    1. Loe H, Theilande E, Jensen SB. Experimental gingivitis in man. J Periodontol. 1965;36:177–87.
    1. Heasman PA. The role of nonsteroidal anti-inflammatory drugs in the management of periodontal disease. J Dent. 1988;16:247–57.
    1. Oringer RJ. Research, Science, Therapy Committee of the American Academy of Periodontology. Modulation of the host response in periodontal therapy. J Periodontol. 2002;3:460–70.
    1. Kirkwood KL, Cirelli JA, Rogers JE, Giannobill WV. Novel host response therapeutic approach to treat periodontal disease. Periodontol 2000. 2007;43:294–315.
    1. Genco RJ. Host responses in periodontal diseases: Current concepts. J Periodontol. 1992;63(Suppl. 4):338–55.
    1. Grossi SG, Zambon JJ, Ho AW, Ho AW, Koch G, Dunford RG, et al. Assessment of risk for periodontal disease. I. Risk indicators for attachment loss. J Periodontol. 1994;65:260–7.
    1. Salvi GE, Lawrence HP, Offenbacher S, Beck JD. Influence of risk factors on the pathogenesis of periodontitis. Periodontol 2000. 1997;14:173–201.
    1. Iqbal Z, Jain N, Jain GK, Talegaonkar S, Ahuja A, Khar RK, et al. Dental therapeutic systems. Recent Pat Drug Deliv Formulation. 2008;2:58–67.
    1. Deporter DA. Periodontal disease part II: Overview of treatment modalities. Can Fam Physician. 1988;34:1391–2.
    1. Freeman E. Periodontal disease part III: Chemotherapeutics. Can Fam Physician. 1988;34:1395–7.
    1. Krayer JW, Leite RS, Kirkwood KL. Non-surgical chemotherapeutic treatment strategies for the management of periodontal diseases. Dent Clin North Am. 2010;54:13–33.
    1. Bader HI. Floss or die: Implications for dental professionals. Den Today. 1998;17:76–82.
    1. Oliver RC, Brown LJ, Loe H. Periodontal diseases in the United States population. J Periodontol. 1998;69:269–78.
    1. Newman MG, Cattabriga M, Etienne D, Flemmig T, Sanz M, Kornman KS, et al. Effectiveness of adjunctive irrigation in early periodontitis. Multi-center evaluation. J Periodontol. 1994;65:224–9.
    1. Fleming TF, Epp B, Funkenhauser Z, Newman MG, Korman KS, Haubitz I, et al. Adjunctive supragingival irrigation with acetylsalicylic acid in periodontal supportive therapy. J Clin Periodontol. 1995;22:427–33.
    1. Brightman LJ, Terezhalmy GT, Greenwell H, Jacobs M, Enlow DH. The effects of a 0.12% chlorhexidine gluconate mouthrinse on orthodontic patients aged 11 through 17 with established gingivitis. Am J Orthod Dentofacial Orthop. 1991;100:324–9.
    1. Pitts G, Brogdon C, Hu L, Masurat T, Pianotti R, Schumann P. Mechanism of action of an antiseptic, anti-order mouthwash. J Dent Res. 1983;62:738–42.
    1. De Boever EH, Loesche WJ. Assessing the contribution of anaerobic microflora of the tongue to oral malador. J Am Dent Assoc. 1995;126:1384–93.
    1. Ciancio SG, Lauciello F, Shibly O, Vitello M, Mather M. The effect of an antiseptic mouthrinse on implant maintenance: Plaque and peri-implant gingival tissues. J Periodontol. 1995;66:962–5.
    1. Greenstein G. Effects of subgingival irrigation on periodontal status. J Periodontol. 1987;58:827–36.
    1. Shiloah J, Hovious LA. The role of subgingival irrigations in the treatment of periodontitis. J Periodontol. 1993;64:835–43.
    1. Lang NP, Raber K. Use of oral irrigators as vehicles for the application of antimicrobial agents in chemical plaque control. J Clin Periodontol. 1981;8:177–88.
    1. Lang NP, Ramseir-Grossman K. Optimal dosage of chlorhexidine digluconate in chemical plaque control when applied by an oral irrigator. J Clin Periodontol. 1981;8:189–202.
    1. Flemmig TG, Newman MG, Doherty FM, Grossman E, Meckel AH, Bakdash MB. Supragingival irrigation with 0.06% chlorhexidine in naturally occuring gingivitis. I. 6 month clinical observations. J Periodontol. 1990;61:112–7.
    1. Boyd RL, Hollander BN, Eakle WS. Comparison of subgingivally placed cannula oral irrigator tip with a supragingivally placed standard irrigator tip. J Clin Periodontol. 1992;19:340–4.
    1. Greenstein G. Effects of subgingival irrigation on periodontal status. J Periodontol. 1987;58:827–36.
    1. Greenstein G. Research, Science and Therapy Committee of the American Academy of Periodontology. The Role of supra- and subgingival irrigation in the treatment of periodontal diseases. J Periodontol. 2005;76:2015–27.
    1. Listgarten MA, Grossberg D, Schwimer C, Vito A, Gaffar A. Effect of subgingival irrigation with tetrapotassium peroxydiphosphate on scaled and untreated periodontal pockets. J Periodontol. 1989;60:4–11.
    1. Southard SR, Drisko CL, Killoy WJ, Cobb CM, Tira DE. The effects of 2% chlorhexidine digluconate irrigation on the levels of Bacteroides gingivalis in periodontal pockets. J Periodontol. 1989;60:302–9.
    1. Lander PE, Newcomb GM, Seymour GJ, Powell RN. The antimicrobial and clinical effects of a single subgingival irrigation of chlorhexidine in advanced periodontal lesions. J Clin Periodontol. 1986;13:74–80.
    1. Watts EA, Newman HN. Clinical effects on chronic periodontis of a simplified system of oral hygiene including subgingival pulsated jet irrigation with chlorhexidine. J Clin Periodontol. 1986;13:666–70.
    1. MacAlpine R, Magnusson I, Kiger R, Crigger M, Garrett S, Egelberg J. Antimicrobial irrigation of deep pockets to supplement oral hygiene instruction and root debridement. I. Biweekly irrigation. J Clin Periodontol. 1985;12:568–77.
    1. Marsh PD. Dental plaque as a biofilm and a microbial community-implications for health and disease. BMC Oral Health. 2006;6(Suppl. 1):S14.
    1. Giusto T. Non-surgical vs. surgical periodontal therapy. New York, USA: SUNY Stonybrook; 1997. p. 1.
    1. Cobb CM. Non-surgical pocket therapy: Mechanical. Ann Periodontol. 1996;1:443–90.
    1. Obeid PR, D’Hoore W, Bercy P. Comparative clinical responses related to the use of various periodontal instrumentation. J Clin Periodontol. 2004;31:193–9.
    1. Serino G, Rosling B, Ramberg P, Socransky SS, Lindhe J. Initial outcome and longterm effect of surgical and nonsurgical treatment of advanced periodontal disease. J Clin Periodontol. 2001;28:910–6.
    1. Cugini MA, Haffajee AD, Smith C, Kent RL, Jr, Socransky SS. The effect of scaling and root planing on the clinical and microbiological parameters of periodontal diseases: 12-month results. J Clin Periodontol. 2000;27:30–6.
    1. Slots J, Rams TE. Antibiotics in periodontal therapy: Advantages and disadvantages. J Clin Periodontol. 1990;17:479–93.
    1. Clifford LR, Needleman IG, Chan YK. Comparison of periodontal pocket penetration by conventional and microultrasonic insets. J Clin Periodontol. 1999;26:124–30.
    1. D’Ercole S, Piccolomini R, Capaldo G, Catamo G, Perinetti G, Guida L. Effectiveness of ultrasonic instruments in the therapy of severe periodontitis: A comparative clinical-microbiological assessment with curettes. New Microbiol. 2006;29:101–10.
    1. Kishida M, Sato S, Ito K. Effects of a new ultra-sonicscaler on fibroblast attachment to root surfaces: A scanning electron microscopy analysis. J Periodontal Res. 2004;39:111–9.
    1. Cobb CM. Clinical significance of non-surgical periodontal therapy: An evidence-based perspective of scaling and root planing. J Clin Periodontol. 2002;29(Suppl. 2):6–16.
    1. Sculean A, Schwarz F, Berakdar M, Romanos GE, Brecx M, Willershausen B. Non-surgical periodontal treatment with a new ultrasonic device (Vector-ultrasonic system) or hand instruments. J Clin Periodontol. 2004;31:428–33.
    1. Goodson JM, Tanner A, McArdle S, Dix K, Watanabe SM. Multicentre evaluation of tetracycline fibre therapy. III. Microbiological response. J Periodontal Res. 1991;26:440–51.
    1. Harper DS, Robinson PJ. Correlation of histometric, microbial and clinical indicators of periodontal disease indicators status before and after root planning. J Clin Periodontal. 1987;14:190–6.
    1. Koshy G, Corbet EF, Ishikawa I. A full-mouth disinfection approach to nonsurgical periodontal therapy and prevention of reinfection from bacterial reservoirs. Periodontol 2000. 2004;36:166–78.
    1. Teughels W, Dekeyser C, Van Essche M, Quirynen M. One-stage, full-mouth disinfection: Fiction or reality? Periodontol 2000. 2009;50:39–51.
    1. Swierkot K, Nonnenmacher CI, Mutters R, Flores-de-Jacoby L, Mengel R. One-stage full-mouth disinfection versus quadrant and full-mouth root planning. J Clin Periodontol. 2009;36:240–9.
    1. Aoki A, Sasaki KM, Watanabe H, Ishikawa I. Lasers in nonsurgical periodontal therapy. Periodontol 2000. 2004;36:59–97.
    1. Matthews DC. Seeing the light-the truth about soft tissue lasers and nonsurgical periodontal therapy. J Can Dent Assoc. 2010;76:a30.
    1. Rajababu P, Reddy Harinath S, Satyanarayana D, Kumar Sunil P. Non surgical periodontal therapy. Ind J Dent Adv. 2009;1:16–9.
    1. Preshaw PM, Hefti AF, Jepsen S, Etienne D, Walker C, Bradshaw MH. Subantimicrobial dose doxycycline as adjunctive treatment for periodontitis. A review. J Clin Periodontol. 2004;31:697–707.
    1. Slots J, Pallasch TJ. Dentist's role in halting antimicrobial resistance. J Dent Res. 1996;75:1338–41.
    1. Vandekerckhove BN, Quirynen M, van Steenberghe D. The use of tetracycline-containing controlled release fibres in the treatment of refractory periodontitis. J Periodontol. 1997;68:353–61.
    1. Pitcher GR, Newman HN, Strahan JD. Access to subgingival plaque by disclosing agents using mouthrinsing and direct irrigation. J Clin Periodontol. 1980;7:300–8.
    1. Gates KA, Grad H, Birek P, Lee PI. A new bioerodible polymer insert for a controlled release of metronidazole. Pharm Res. 1994;11:1605–9.
    1. Greenstein G. Local drug delivery in the treatment of periodontal diseases: Assessing the clinical significance of the results. J Periodontol. 2006;77:565–78.
    1. Listgarten MA, Lindhe J, Hellden L. Effect of tetracycline and or scaling on human periodontal disease, Clinical, microbiological and histological observations. J Clin Periodontol. 1978;5:246–71.
    1. Lindhe J, Liljenberg B, Adielsson B. Effect of long-term tetracycline therapy on human periodontal disease. J Clin Periodontol. 1983;10:590–601.
    1. Goodson JM. Pharmacokinetic principles controlling efficacy of oral therapy. J Dent Res. 1989;68:1625–32.
    1. Jones DS, Woolfson AD, Djokic J, Coulter WA. Development and mechanical characterization of bioadhesive semi-solid, polymeric systems containing tetracycline for the treatment of periodontal diseases. Pharm Res. 1996;13:1734–8.
    1. Maze GI, Reinhardt RA, Payne JB, Maze C, Baker RA, Bouwsma OJ, et al. Gingival fluid tetracycline release from bioerodible gels. J Clin Periodontol. 1996;23:133–6.
    1. Polson AM, Stoller NH, Hanes PJ, Bandt CL, Garrett S, Southard GL. Two multi-center trials assessing the clinical efficacy of 5% sanguinarine in a biodegradable drug delivery system. J Clin Periodotol. 1996;23:782–8.
    1. Jones DS, Woolfson AD, Brown AF, O’neill MJ. Mucoadhesive, syringeable drug delivery systems for controlled application of metronidazole to the periodontal pocket: In vitro release kinetics, syringeability, mechanical and mucoadhesive properity. J Control Rel. 1997;49:71–9.
    1. Noyan U, Yilmaz S, Kuru B, Kadir T, Acar O, Büget E. A clinical and microbiological evaluation of systemic and local metronidazole delivery in adult periodontitis patients. J Clin Periodontol. 1997;24:158–65.
    1. Polson AM, Garrett S, Stoller NH, Bandt CL, Hanes PJ, Killoy WJ, et al. Multi-center comparative evaluation of subgingivally delivered sanguinarine and doxycycline in the treatment of periodontitis. II. Clinical results. J Periodontol. 1997;68:119–26.
    1. Wolinsky LE, Camargo PM, Polson A, Ryder M, Garrett S. The significance of prior mechanical therapy for changes of periodontal status achieved by local delivery of a doxycyclinehyclate containing gel. J Clin Periodotol. 2001;28:1115–20.
    1. Leitão RF, Rocha FA, Chaves HV, Lima V, Cunha FQ, Ribeiro RA, et al. Locally applied isosorbide decreases bone resorption in experimental periodontitis in rats. J Periodontol. 2004;75:1227–32.
    1. Akncbay H, Senel S, Ay ZY. Application of chitosan gel in the treatment of chronic periodontitis. J Biomed Mat Res Part B. J Biomed Mater Res B Appl Biomater. 2007;80:290–6.
    1. Bruschi ML, Jones DS, Panzeri H, Gremião MP, de Freitas O, Lara EH. Semisolid systems containing propolis for the treatment of periodontal disease: In vitro release kinetics, syringeability, rheological, textural, and mucoadhesive properties. J Pharm Sci. 2007;96:2074–89.
    1. Pradeep AR, Sagar SV, Daisy H. Clinical and microbiologic effects of subgingivally delivered 0.5% azithromycin in the treatment of chronic periodontitis. J Periodontol. 2008;79:2125–35.
    1. Bogren A, Teles RP, Torresyap G, Haffajee AD, Socransky SS, Wennström JL. Locally delivered doxycycline during supportive periodontal therapy: A 3-year study. J Periodontol. 2008;79:827–35.
    1. Morris MS, Lee Y, Lavin MT, Giannini PJ, Schmid MJ, Marx DB, et al. Injectable simvastatin in periodontal defects and alveolar ridges: Pilot studies. J Periodontol. 2008;79:1465–73.
    1. Rassameemasmaung S, Sirikulsathean A, Amornchat C, Maungmingsook P, Rojanapanthu P, Gritsanaphan W. Topical application of Garcinia mangostana L. pericarp gel as an adjunct to periodontal treatment. Complement Ther Med. 2008;16:262–7.
    1. Tomasi C, Koutouzis T, Wennström JL. Locally delivered doxycycline as an adjunct to mechanical debridement at retreatment of periodontal pockets. J Periodontol. 2008;79:431–9.
    1. Paolantonio M, D’Ercole S, Pilloni A, D’Archivio D, Lisanti L, Graziani F, et al. Clinical, microbiologic, and biochemical effects of subgingival administration of a Xanthan-based chlorhexidine gel in the treatment of periodontitis: A randomized multicenter trial. J Periodontol. 2009;80:1479–92.
    1. Dabhi MR, Nagori SA, Gohel MC, Parikh RK, Sheth NR. Formulation development of smart gel periodontal drug delivery system for local delivery of chemotherapeutic agents with application of experimental design. Drug Deliv. 2010;17:520–31.
    1. Ji QX, Zhao QS, Deng J, Lü R. A novel injectable chlorhexidine thermosensitive hydrogel for periodontal application: Preparation, antibacterial activity and toxicity evaluation. J Mater Sci Mater Med. 2010;21:2435–42.
    1. Pradeep AR, Thorat MS. Clinical effect of subgingivally delivered simvastatin in the treatment of patients with chronic periodontitis: A randomized clinical trial. J Periodontol. 2010;81:214–22.
    1. Yaffe A, Herman A, Bahar H, Binderman I. Combined local application of tetracycline and bisphosphonate reduces alveolar bone resorption in rats. J Periodontol. 2003;74:1038–42.
    1. Jones DS, Woolfson AD, Brown AF, Coulter WA, McClelland C, Irwin CR. Design, characterisation and preliminary clinical evaluation of a novel mucoadhesive topical formulation containing tetracycline for the treatment of periodontal disease. J Control Release. 2000;67:357–68.
    1. Murakami S, Takayama S, Kitamura M, Shimabukuro Y, Yanagi K, Ikezawa K, et al. Recombinant human basic fibroblast growth factor (bFGF) stimulates periodontal regeneration in class II furcation defects created in beagle dogs. J Periodontal Res. 2003;38:97–103.
    1. Hirasawa M, Hayashi K, Takada K. Measurement of peptidase activity and evaluation of effectiveness of administration of minocycline for treatment of dogs with periodontitis. Am J Vet Res. 2000;11:1349–52.
    1. Azmak N, Atilla G, Luoto H, Sorsa T. The effect of subgingival controlled-release delivery of chlorhexidine chip on clinical parameters and matrix metalloproteinase-8 levels in gingival crevicular fluid. J Periodontol. 2002;73:608–15.
    1. Parthasarathy V, Manavalan R, Mythili R, Siby CT, Jeya M. Ethyl cellulose and polyethylene glycol-based sustained-release sparfloxacin chip: An alternative therapy for advanced periodontitis. Drug Dev Ind Pharm. 2002;28:849–62.
    1. Kasaj A, Chiriachide A, Willershausen B. The adjunctive use of a controlled-release hlorhexidine chip following treatment with a new ultrasonic device in supportive periodontal therapy: A prospective, controlled clinical study. Int J Dent Hyg. 2007;5:225–31.
    1. Duarte Fde F, Lotufo RF, Pannuti CM. Local delivery of chlorhexidine gluconate in patients with aggressive periodontitis. J Int Acad Periodontol. 2008;10:31–5.
    1. Paolantonio M, D’Angelo M, Grassi RF, Perinetti G, Piccolomini R, Pizzo G, et al. Clinical and microbiologic effects of subgingival controlled-release delivery of chlorhexidine chip in the treatment of periodontitis: A multicenter study. J Periodontol. 2008;79:271–82.
    1. Yamagami H, Takamori A, Sakamoto T, Okada H. Intrapocket chemotherapy in adult periodontitis using a new controlled-release insert containing ofloxacin (PT-01) J Periodontol. 1992;63:2–6.
    1. Barat R, Srinatha A, Pandit JK, Ridhurkar D, Balasubramaniam J, Mittal N, et al. Niridazole biodegradable inserts for local long-term treatment of periodontitis: Possible new life for an orphan drug. Drug Deliv. 2006;13:365–73.
    1. Barat R, Srinatha A, Pandit JK, Mittal N, Anupurba S. Ethylcellulose inserts of an orphan drug for periodontitis: Preparation, in vitro, and clinical studies. Drug Deliv. 2007;14:531–8.
    1. Friedman M, Golomb G. New sustained release dosage form of chlorhexidine for dental use. J Periodontal Res. 1982;17:323–8.
    1. Addy M, Langeroudi M. Comparison of the immediate effects on the sub-gingival microflora of acrylic strips containing 40% chlorhexidine, metronidazole or tetracycline. J Clin Periodontol. 1984;11:379–86.
    1. Noguchi T, Izumizawa K, Fukuda M, Kitamura S, Suzuki Y, Ikura H. New method for local drug delivery using resorbable base material in periodontal therapy. Bull Tokyo Med Dent Univ. 1984;31:145–53.
    1. Addy M, Hassan H, Moran J, Wade W, Newcombe R. Use of antimicrobial containing acrylic strips in the treatment of chronic periodontal disease. A three month follow-up study. J Periodontol. 1988;59:557–64.
    1. Deasy PB, Collins AE, MacCarthy DJ, Russell RJ. Use of strips containing tetracycline hydrochloride or metronidazole for the treatment of advanced periodontal disease. J Pharm Pharmacol. 1989;41:694–9.
    1. Fanas Abu SH, Drucker DB, Hull PS. Evaluation of acrylic strips containing amoxycillin with clavulanic acid for local drug delivery. J Dent. 1991;19:92–6.
    1. Corry D, Moran J. Assessment of acrylic bone cement as a local delivery vehicle for the application of non-steroidal anti-inflammatory drugs. Biomaterials. 1998;19:1295–301.
    1. Friesen LR, Williams KB, Krause LS, Killoy WJ. Controlled local delivery of tetracycline with polymer strips in the treatment of periodontitis. J Periodontol. 2002;73:13–9.
    1. Hirasawa M, Takada K, Makimura M, Otake S. Improvement of periodontal status by green tea catechin using a local delivery system: A clinical pilot study. J Periodontal Res. 2002;37:433–8.
    1. Leung WK, Jin L, Yau JY, Sun Q, Corbet EF. Microflora cultivable from minocycline strips placed in persisting periodontal pockets. Arch Oral Biol. 2005;50:39–48.
    1. Bromberg LE, Braman VM, Rothstein DM, Spacciapoli P, O’Connor SM, Nelson EJ, et al. Sustained release of silver from periodontal wafers for treatment of periodontitis. J Control Release. 2000;31:63–72.
    1. Golomb G, Friedman M, Soskolne A, Stabholz A, Sela MN. Sustained release device containing metronidazole for periodontal use. J Dent Res. 1984;63:1149–53.
    1. Azoury R, Elkayam R, Friedman M. Nuclear magnetic resonance study of an ethyl cellulose sustained-release delivery system. II. Release rate behavior of tetracycline. J Pharm Sci. 1988;77:428–31.
    1. Elkayam R, Friedman M, Stabholz A, Soskolne AW, Sela MN, Golub L. Sustained release device containing minocycline for local treatment of periodontal disease. J Control Release. 1988;7:231–6.
    1. Minabe M, Uematsu A, Nishijima K, Tomomatsu E, Tamura T, Hori T, et al. Application of a local drug delivery system to periodontal therapy. I. Development of collagen preparations with immobilized tetracycline. J Periodontol. 1989;60:113–7.
    1. Kyun KD, Yun KS, Young JS, Pyoung CC, Heui SS. Development of minocycline containing polycaprolactone film as a local drug delivery. Taehan Chikkwa Uisa Hyophoe Chi. 1990;28:279–90.
    1. Steinberg D, Friedman M, Soskolne A, Sela MN. A new degradable controlled release device for treatment of periodontal disease: In vitro release study. J Periodontol. 1990;61:393–8.
    1. Higashi K, Matsushita M, Morisaki K, Hayashi S, Mayumi T. Local drug delivery systems for the treatment of periodontal disease. J Pharmacobiodyn. 1991;14:72–81.
    1. Agarwal RK, Robinson DH, Maze GI, Reinhardt RA. Development and characterization of tetracycline–poly (lactide/glycolide) films for treatment of periodontitis. J Control Release. 1993;23:137–46.
    1. Maze GI, Reinhardt RA, Agarwal RK, Dyer JK, Robinson DH, DuBoism LM, et al. Response to intracrevicular controlled delivery of 25% tetracycline from poly(lactide/glycolide) film strips in SPT patients. J Clin Periodontol. 1995;22:860–7.
    1. Dedeian VR, Solov’eva NI, Ezikian TI, Medvedeva IA. The treatment of periodontal diseases using Diplen-Denta films with chlorhexidine (a clinico-laboratory study) Stomatologiia (Mosk) 1997;76:18–22.
    1. Vasavada RC, Junnarkar GH. Release of metronidazole from poly (ortho ester) matrices. Proc. Int Symp Controlled Release Bioact Mater. 1997;24:499–500.
    1. Goffin G. Efficacy of sustained local delivery of chlorhexidine Periochip as an adjuvant to scaling and root planning in the treatment of chronic periodontal disease. Int Dent Rev. 1998;18:1–18.
    1. Ozmeriç N, Ozcan G, Haytaç CM, Alaaddinoğlu EE, Sargon MF, Senel S. Chitosan film enriched with an antioxidant agent, taurine, in fenestration defects. J Biomed Mater Res. 2000;51:500–3.
    1. Perugini P, Genta I, Conti B, Modena T, Pavanetto F. Periodontal delivery of ipriflavone: New chitosan/PLGA film delivery system for a lipopholc drug. Int J Pharm. 2003;252:1–9.
    1. Cetin EO, Buduneli N, Atlihan E, Kirilmaz L. In vitro studies on controlled-release cellulose acetate films for local delivery of chlorhexidine, indomethacin, and meloxicam. J Clin Periodontol. 2004;31:1117–21.
    1. Cetin EO, Buduneli N, Atlihan E, Kirilmaz L. In vitro studies of a degradable device for controlled-release of meloxicam. J Clin Periodontol. 2005;32:773–7.
    1. Ahuja A, Ali J, Rahman S. Biodegradable periodontal intrapocket device containing metronidazole and amoxycillin: Formulation and characterization. Pharmazie. 2006;61:25–9.
    1. 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:E75.
    1. Wang LC, Chen XG, Zhong DY, Xu QC. Study on poly(vinyl alcohol)/carboxymethyl-chitosan blend film as local drug delivery system. J Mater Sci Mater Med. 2007;18:1125–33.
    1. Rodriguez-Garcia A, Galan-Wong LJ, Arevalo-Niño K. Development and in vitro evaluation of biopolymers as a delivery system against periodontopathogen microorganisms. Acta Odontol Latinoam. 2010;23:158–63.
    1. Chang CY, Yamada S. Evaluation of the regenerative effect of a 25% doxycycline-loaded biodegradable membrane for guided tissue regeneration. J Periodontol. 2000;71:1086–93.
    1. Kurtiş B, Unsal B, Cetiner D, Gültekin E, Ozcan G, Celebi N, et al. Effect of Polylactide/Glycolide (PLGA) Membranes Loaded With Metronidazole on Periodontal Regeneration Following Guided Tissue Regeneration in Dogs. J Periodontol. 2002;73:694–700.
    1. Goodson JM, Haffajee A, Socransky SS. Periodontal therapy by local delivery of tetracycline. J Clin Periodontol. 1979;6:83–92.
    1. Coventry J, Newman HN. Experimental use of a slow release device employing chlorhexidine gluconate in areas of acute periodontal inflammation. J Clin Periodontol. 1982;9:129–33.
    1. Tonetti M, Cugini MA, Goodson JM. Zero-order delivery with periodontal placement of tetracycline-loaded ethylene vinyl acetate fibres. J Periodontal Res. 1990;25:243–9.
    1. Demirel K, Yalçin F, Polat E, Onan U, Meriç H, Altas K. Release kinetics of 25% tetracycline hydrochloride-loaded ethylene vinyl acetate fibers. Periodontal Clin Invest. 1999;21:6–9.
    1. Sakellari D, Vouros I, Konstantinidis A. The use of tetracycline fibres in the treatment of generalised aggressive periodontitis: Clinical and microbiological findings. J Int Acad Periodontol. 2003;5:52–60.
    1. Aimetti M, Romano F, Torta I, Cirillo D, Caposio P, Romagnoli R. Debridement and local application of tetracycline-loaded fibres in the management of persistent periodontitis: Results after 12 months. J Clin Periodontol. 2004;31:166–72.
    1. Paquette DW. Minocycline microspheres: A complementary medical-mechanical model for the treatment of chronic periodontitis. Compend Contin Educ Dent. 2002;23:15–21.
    1. Williams RC, Paquette DW, Offenbacher S, Adams DF, Armitage GC, Bray K, et al. Treatment of periodontitis by local administration of minocycline microspheres: A controlled trial. J Periodontol. 2001;72:1535–44.
    1. Arica B, Aksungur P, Fienel S, Kas SH, Sargon MF, Hincal Atilla AA. Natamycin loaded chitosan microspheres for periodontal therapy. J Fac Pharm. 2003;23:77–84.
    1. Jeyanthi R, Akiyama A, Roberts FD, VanHamont J, Friden P. One-month controlled release of an antimicrobial peptide from biodegradable poly(lactide/glycolide) microspheres for the treatment of periodontitis. Proc. Int Symp Controlled Release Bioact mater. 1997;24:883–4.
    1. Kockisch S, Rees GD, Tsibouklis J, Smart JD. Mucoadhesive, triclosan loaded polymer microspheres for application to the oral cavity: Preparation and the controlled release characteristics. Eur J Pharm Biopharm. 2005;59:207–16.
    1. Samdancioglu S, Calis S, Sumnu M, Hincal Atilla A. Formulation and in vitro evaluation of bisphosphonate loaded microspheres for implantation in osteolysis. Drug Dev Ind Pharm. 2006;32:473–81.
    1. Samati Y, Yüksel N, Tarimci N. Preparation and characterization of poly (D,L-Lactic-Co-Glycolic Acid) microspheres containing flurbiprofen sodium. Drug Deliv. 2006;13:105–11.
    1. Bland PS, Goodson JM, Gunsolley JC, Grossi SG, Otomo-Corgel J, Doherty F, et al. Association of antimicrobial and clinical efficacy: Periodontitis therapy with minocycline microspheres. J Int Acad Periodontol. 2010;12:11–9.
    1. Esposito E, Cortesi R, Cervellati F, Menegatti E, Nastruzzi C. Biodegradable microparticles for sustained delivery of tetracycline to the periodontal pocket: Formulatory and drug release studies. J Microencapsul. 1997;14:175–87.
    1. Mundargi RC, Srirangrajan S, Agnihotri SA, Sangamesh A, Patil SA, Ravindra S, et al. Development and evaluation of novel biodegradable microsphere based on Poly (D,L-lactide-co-glycolide)and poly(€ -caprolactone) for contolled delivery of doxycycline in the treatment of periodontal pocket: In vitro and in vivo studies. J Control Release. 2007;119:59–68.
    1. Baker RW, Krisko EA, Kochinke F. A controlled release drug delivery system for periodontal pocket. International symposium on controlled release Bioactive Materials USA. Controlled Release Soc. 1988;140:238a–b.
    1. Bruschi ML, De Freitas O, Lara EH, Panzeri H, Gremião MP, Jones DS. Precursor system of liquid crystalline phase containing propolis microparticles for the treatment of periodontal disease: Development and characterization. Drug Dev Ind Pharm. 2008;34:267–78.
    1. Yeom HR, Park YJ, Lee SJ, Rhyu IC, Chung CP, Nisengard RJ. Clinical and microbiological effects of minocycline-loaded microcapsules in adult periodontitis. J Periodontol. 1997;68:1102–9.
    1. Pinon-Segundo E, Ganem-Quintanar A, Alonso-Perez V, Quintanar-Guerrero D. Preparation and characterization of triclosan nanoparticles for periodontal treatment. Int J Pharm. 2005;294:217–32.
    1. Moulari B, Lboutounne H, Chaumont JP, Guillaume Y, Millet J, Pellequer Y. Potentiation of the bactericidal activity of harungana madagascariensis lam. Ex poir. (Hypericaceae) leaf extract against oral bacteria using poly (d, l-lactide-co-glycolide) nanoparticles: In vitro study. Acta Odontol Scand. 2006;64:153–8.
    1. Bakó J, Szepesi M, Márton I, Borbély J, Hegedûs C. Synthesis of nanoparticles for dental drug delivery systems. Fogorv Sz. 2007;100:109–13.
    1. Dung TH, Lee SR, Han SD, Kim SJ, Ju YM, Kim MS, et al. Chitosan-TPP nanoparticle as a release system of antisense oligonucleotide in the oral environment. J Nanosci Nanotechnol. 2007;7:3695–9.
    1. Jones MN, Kaszuba M. Polyhydroxy-mediated interactions between liposomes and bacterial biofilms. Biochim Biophys Acta. 1994;1193:48–54.
    1. Jones MN, Song YH, Kaszuba M, Reboiras MD. The interaction of phospholipid liposomes with bacteria and their use in the delivery of bactericides. J Drug Target. 1997;5:25–34.
    1. Vyas SP, Sihorkar V, Dubey PK. Preparation, characterization and in vitro antimicrobial activity of metronidazole bearing lectinized liposomes for intra-periodontal pocket delivery. Pharmazie. 2001;56:554–60.
    1. Tamimi F, Torres J, Bettini R, Ruggera F, Rueda C, López-Ponce M, et al. Doxycycline sustained release from brushite cements for the treatment of periodontal diseases. J Biomed Mater Res A. 2008;85:707–14.
    1. Vandekerckhove BN, Van Steenberghe D, Tricio J, Rosenberg D, Encarnacion M. Efficacy on supragingival plaque control of cetylpyridinium chloride in a slow-release dosage form. J Clin Periodotol. 1995;22:824–9.
    1. Jadhav BK, Khandelwal KR, Ketkar AR, Pisal SS. Formulation and evaluation of mucoadhesive tablets containing eugenol for the treatment of periodontal diseases. Drug Dev Ind Pharm. 2004;30:195–203.
    1. Fehér A, Urbán E, Eros I, Szabó-Révész P, Csányi E. Lyotropic liquid crystal preconcentrates for the reatment of periodontal disease. Int J Pharm. 2008;358:23–6.
    1. Kozlovsky A, Sintov A, Moldovan M, Tal H. Inhibition of plaque formation by local application of a degradable controlled release system containing cetylpyridinium chloride. J Clin Periodontol. 1994;21:32–7.
    1. Tallury P, Alimohammadi N, Kalachandra S. Poly(ethylene-co-vinyl acetate) copolymer matrix for delivery of chlorhexidine and acyclovir drugs for use in the oral environment: Effect of drug combination, copolymer composition and coating on the drug release rate. Dental Mater. 2007;23:404–9.
    1. Esposito E, Carotta V, Scabbia A, Trombelli A, Antona PD, Menegatti E, et al. Comparative analysis of tetracycline- containing dental gels: Poloxamer- and monoglyceride- based formulation. Int J Pharm. 1996;142:9–23.
    1. Emami J. In vitro - In vivo Correlation: From Theory to Applications. J Pharm Pharm Sci. 2006;9:169–89.
    1. Hattingh J, Ho E. The concentration of proteins in human gingival crevicular fluid. J Periodontal Res. 1980;15:90–5.
    1. Cimasoni G. Crevicular fluid update. Vol. 12. Swizerland: Karger Publishing Co; 1983. p. 71.
    1. Kobayashi K, Kobayashi K, Soeda W, Watanabe T. Gingival cervical pH in experimental gingivitis and occlusal trauma in man. J Periodontol. 1998;69:1036–43.
    1. Bromberg LE, Buxton DK, Friden PM. Novel periodontal drug delivery system for treatment of periodontitis. J Control Release. 2001;71:251–9.
    1. Shani S, Friedman M, Steinberg D. In vitro assessment of the antimicrobial activity of a local sustained release device containing Amine fluorides forvthe treatment of oral infectious diseases. Diagn Microbiol Infect Dis. 1998;30:93–7.
    1. Ahuja A, Ali J, Rahman S, Shareef A, Khar RK. Targeted retentive device for oro-dental infections: Formulation and development. Int J Pharm. 2003;259:47–55.
    1. Roskos KV, Fritzinger BK, Rao SS, Armitage GC, Heller J. Development of a drug delivery system for the treatment of periodontal disease based on bioerodible poly (ortho easters) Biomater. 1995;16:313–7.
    1. Okonogi S, Khongkhunthain S, Bunyaratavej P, Thusaphorn T, Umpriwan R. Development of local injectable dental gel: The influence of certain additives on physicochemical properties of glycerylmonooleate-based formulations. Drug Dev Ind Pharm. 2004;30:347–57.
    1. Periole L, Amborgi V, Rubini D, Giovagnoli S, Ricci M, Balsi P, Rossi C. Novel mucoiadhesive buccal formulation containing metronidazole for the treatment of periodontal disease. J Control Release. 2004;95:521–33.
    1. Kelly HM, Deasy PB, Ziaka E, Claffey N. Formulation and preliminary in vivo dog studies of a novel drug delivery system for the treatment of periodontitis. Int J Pharm. 2004;274:167–83.
    1. Yue IC, Poff J, Cortés ME, Sinisterra RD, Faris CB, Hildgen P, et al. A novel polymeric chlorhexidine delivery device for the treatment of periodontal disease. Biomaterials. 2004;25:3743–50.
    1. Liuy DZ, Chenz WZ, Lee CP, Wuz SL, Wangz YC, Chung TW. Effects of alginate coated on PLGA microspheres for delivery tetracycline hydrochloride to periodontal pockets. J Microencapsul. 2004;21:643–52.
    1. Weinberg MA, Bral M. Laboratory animal models in periodontology. J Clin Periodontol. 1999;26:335–40.
    1. Krygier G, Genco R, Mashimo P, Hausman E. Experimental gingivitis in Macaca Speciosa monkeys: Clinical, bacteriologic and histologic similarities to human gingivitis. J Periodontol. 1973;44:454–463.
    1. Schou S, Holmstrup P, Kornman KS. Non-Human primates used in studies of periodontal disease pathogenesis: A review of the literature. J Periodontol. 1993;64:497–508.
    1. Brecx M, Nalbandiam J, Ooya K, Kornman K, Robertson R. Morphological studies on periodontal disease in the Cynomolgus monkey (II). Light microscopic observations on ligature induced Periodontitis. J Periodontal Res. 1985;20:165–75.
    1. Polson AM. Trauma and progression of marginal periodontitis in squirrel monkeys (II). Co-destructive factors or periodontitis and mechanicallyproduced injury. J Periodontal Res. 1974;9:108–13.
    1. Caton JG, Kowalski CJ. Primate model for testing periodontal treatment procedures (II). Production of contralaterally similar lesions. J Periodontol. 1976;46:506–10.
    1. Giannobile WV, Finkelman RD, Lynch SE. Comparison of canine and non-human primate animal models for periodontal regenerative therapy. Result following a single administration of PDGF/IGF-I. J Periodontol. 1994;65:1158–68.
    1. Caton J, Mota L, Gandini L, Laskaris B. Non-human primate models for testing the efficacy and safety of periodontal regenerative procedures. J Periodontol. 1994;65:1143–50.
    1. Fritz EF, Braswell LD, Koth D, Jeff coat M, Reddy M, Cotsonis G. Experimental peri-implantitis in consecutively placed, loaded root-form and plateform implants in adult Macaca mulatta monkeys. J Periodontol. 1997;68:1131–5.
    1. Navia JM. Animal models in dental research. Vol. 169. Alabama: University of Alabama Press; 1977. pp. 170–8.
    1. Listgarten MA. Similarity of epithelial relationships in the gingiva of rat and man. J Periodontol. 1975;46:677–80.
    1. Irving J, Socransky S. Histological changes in experimental periodontal disease in gnotobiotic rats and conventional hamsters. J Periodontal Res. 1974;9:73–80.
    1. Socransky S, Hubersak C, Propas D. Induction of periodontal destruction in gnotobiotic rats by a human oral strain of Actinomyces Naeslundii. Arch Oral Biol. 1970;15:993–5.
    1. Klausen B, Hougen H, Eriksen W, Fiehn N. Induction of periodontal bone loss in athymic (nude) rats monoinfected with streptococcus mutans. J Periodontal Res. 1986;21:5–12.
    1. Crawford J, Taubman M, Smith D. The natural history of periodontal bone loss in germfree and gnotobiotic rats infected with periodontophathic microorganisms. J Periodontal Res. 1978;8:57–62.
    1. Heijl L, Wennstrom J, Lindhe J, Socransky SS. Periodontal disease in gnotobiotic rats. J Periodontal Res. 1980;15:405–19.
    1. Baer PM, Stephan R, White C. Studies on experimental calculus formation in the rat. J Periodontol. 1961;32:190–6.
    1. Jordan H, Keyes P. Aerobic, grampositive, filamentous bacteria as etiologic agents of experimental periodontal disease in Hamster. Arch Oral Bio. 1964;9:401–14.
    1. Keyes P, Jordan H. Periodontal lesions in Syrian hamster (III) findings related to an infectious and transmissible component. Arch Oral Biol. 1964;9:377–400.
    1. Attstrom R, Graf-De Beer M, Schroeder H. Clinical and histologic characteristics of normal gingival in dogs. J Periodontal Res. 1975;10:115–27.
    1. Ericsson I, Lindhe J, Rylander H, Okamoto H. Experimental periodontal breakdown in the dog. Scandinavia J Res. 1975;83:189–92.
    1. Gad T. Periodontal disease in dogs (I). Clinical investigation. J Periodontal Res. 1968;3:268–72.
    1. Hull PS, Soames JV, Davies RM. Periodontal disease in a Beagle dog colony. J Comp Path. 1974;84:143–51.
    1. Lindhe J, Hamp S, Löe H. Plaque induced periodontal disease in Beagle Dogs, A 4-year clinical roentgenographical and histometrical study. J Periodontal Res. 1975;10:243–55.
    1. Soames J, Davies R. Lymphocytemacrophage and lymphocyte-lymphocytem associations in early gingivitis in Beagle dogs. J Periodontal Res. 1980;15:341–4.
    1. Schroeder H, Lindhe J. Conversion of established gingivitis in the dog into destructive periodontitis. Arch Oral Biol. 1975;20:775–82.
    1. Lindhe J, Rylander H. Experimental gingivitis in young dogs. Scandinavia J Dent Res. 1975;83:314–26.
    1. Harper DS, Mann PH, Regnier S. Measurement of dietary effects upon calculus accumulation rates in the domestic ferret. J Dent Res. 1990;69:447–50.
    1. King JD, Gimson AP. Experimental investigations of periodontal disease in the ferret and related lesions in man. Br Dent J. 1947;83:126–7.
    1. Fischer RG, Klinge B. Clinical and histological evaluation of ligature-induced periodontitis in the domestic ferret. J Clin Periodontol. 1994;21:230–9.
    1. Medlicott NJ, Rathbone MJ, Tucker IG, Holborow HW. Delivery systems for the administration of drugs to the periodontal pocket. Adv Drug Del Rev. 1994;13:181–203.
    1. Ainamo J. Epidemiology of periodontal disease. In: Lindhe J, editor. Textbook of clinical periodontology. Munksgaard: Copenhagen; 1989. pp. 70–91.
    1. Nyman S, Lindhe J. Examination of patients with periodontal disease. In: Lindhe J, editor. Textbook of clinical periodontology. Munksgaard: Copenhagen; 1989. pp. 310–22.
    1. Klinge B, Kuvatanasuhati J, Attström R, Kalfas S, Edwardsson S. The effect of topical metronidazole therapy on experimentally-induced periodontitis in the beagle dog. J Clin Periodontol. 1992;19:702–7.
    1. Kozlovsky A, Sintov A, Zubery Y, Tal H. Inhibition of plaque formation and gingivitis in beagle dogs by topical use of a degradable controlled-release system containing chlorhexidine. J Dent Res. 1992;71:1577–81.
    1. Polson AM, Southard GL, Dunn RL, Yewey GL, Godowski KC, Polson AP, et al. Periodontal pocket treatment in beagle dogs using subgingival doxycycline from a biodegradable system. I. Initial clinical responses. J Periodontol. 1996;67:1176–84.
    1. Hayashi K, Takada K, Hirasawa M. Clinical and microbiological effects of controlled-release local delivery of minocycline on periodontitis in dogs. Am J Veterinary. 1998;59:464–7.
    1. Sato Y, Kikuchi M, Ohata N, Tamura M, Kuboki Y. Enhanced cementum formation in experimentally induced cementum defects of the root surface with the application of recombinant basic fibroblast growth factor in collagen gel in vivo. J Periodontol. 2004;75:243–8.
    1. Anzai J, Kitamura M, Nozaki T, Nagayasu T, Terashima A, Asano T, Murakami S. Effects of concomitant use of fibroblast growth factor (FGF)-2 with beta-tricalcium phosphate (β-TCP) on the beagle dog 1-wall periodontal defect model. Biochem Biophys Res Commun. 2010;403:345–50.
    1. Luan Q, Desta T, Chehab L, Sanders VJ, Plattner J, Graves DT. Inhibition of experimental periodontitis by a topical boron-based antimicrobial. J Dent Res. 2008;87:148–52.
    1. Houri-Haddad Y, Halabi A, Soskolne WA. Inflammatory response to chlorhexidine, minocycline HCl and doxycycline HCl in an in vivo mouse model. J Clin Periodontol. 2008;35:783–8.
    1. Vandekerckhove BN, Quirynen M, Van Steeberghe D. The use of localy delivered minocycline in the treatment of chronic periodontitis. A review of literature. J Clin Periodontol. 1998;25:964–8.
    1. Newman HN. Plaque and chronin inflammatory disease. A question of ecology. J Clin Periodontol. 1990;17:533–44.
    1. Cheristersson LA, Zambon JJ, Genco RJ. Dental bacterial plaques. Nature and role in periodontal disease. J Clin Periodontol. 1991;11:21–32.
    1. Ikinci G, Senel S, Akincibay H, Kaş S, Erciş S, Wilson CG, Hincal AA. Effect of chitosan on a periodontal pathogen Porphyromonas gingivalis. Int J Pharm. 2002;235:121–7.
    1. Govender S, Pillay V, Chetty DJ, Essack SY, Dangor CM, Govender T. Optimisation and characterisation of bioadhesive controlled release tetracycline microspheres. Int J Pharm. 2005;306:24–40.
    1. Ahuja A, Rahman S, Ali A, Chaudhry R. Effect of Dental Films containing amoxyciline and metronidazole on periodontal pathogens: Microbiological response. Pharmazie. 2003;58:716–20.

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