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Focal Drug Delivery for Management of Oral Infections

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Part of the Advances in Delivery Science and Technology book series (ADST)

Abstract

Infection-related dental diseases, common in humans, include caries lesions, periodontal diseases, and endodontic infections. A variety of pharmaceutical dosage forms are used to prevent and treat oral diseases, most of them delivered focally and resulting in a local effect. The latest insights from the field of antimicrobial focal drug delivery has led to the development of various systems designed to effectively combat infections in the oral cavity, with minimal side effects. In the present chapter, the etiology of common oral diseases, characterization of infection–host interactions in oral disease, and classic dental treatment modalities are presented. We discuss the organization of oral microbes into biofilms and the intrinsic susceptibility characteristics of oral tissues, as well as the advantages of controlled focal drug delivery. The recent development of various novel technologies for the prevention, control, and treatment of oral infections are considered, including controlled focal delivery modalities.

Keywords

  • Dental Caries
  • Root Canal
  • Mutans Streptococcus
  • Amorphous Calcium Phosphate
  • Mouth Rinse

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Watnick P, Kolter R (2000) Biofilm, city of microbes. J Bacteriol 182(10):2675–2679

    CAS  PubMed Central  PubMed  Google Scholar 

  2. Amano A, Nakagawa I, Hamada S (1999) Studying initial phase of biofilm formation: molecular interaction of host proteins and bacterial surface components. Methods Enzymol 310:501–513

    CAS  PubMed  Google Scholar 

  3. Marsh PD, Bradshaw DJ (1995) Dental plaque as a biofilm. J Ind Microbiol 15(3):169–175

    CAS  PubMed  Google Scholar 

  4. Hannig C, Hannig M (2009) The oral cavity–a key system to understand substratum-dependent bioadhesion on solid surfaces in man. Clin Oral Investig 13(2):123–139

    PubMed  Google Scholar 

  5. Herrera D et al (2008) Antimicrobial therapy in periodontitis: the use of systemic antimicrobials against the subgingival biofilm. J Clin Periodontol 35(8 Suppl):45–66

    CAS  PubMed  Google Scholar 

  6. Kolenbrander PE (2000) Oral microbial communities: biofilms, interactions, and genetic systems. Annu Rev Microbiol 54:413–437

    CAS  PubMed  Google Scholar 

  7. Kolenbrander PE et al (2006) Bacterial interactions and successions during plaque development. Periodontol 2000 42:47–79

    PubMed  Google Scholar 

  8. Hardie JM (1992) Oral microbiology: current concepts in the microbiology of dental caries and periodontal disease. Br Dent J 172(7):271–278

    CAS  PubMed  Google Scholar 

  9. Zitzmann NU, Berglundh T (2008) Definition and prevalence of peri-implant diseases. J Clin Periodontol 35(8 Suppl):286–291

    PubMed  Google Scholar 

  10. Donlan RM (2000) Role of biofilms in antimicrobial resistance. ASAIO J 46(6):S47–S52

    CAS  PubMed  Google Scholar 

  11. Lewis K (2001) Riddle of biofilm resistance. Antimicrob Agents Chemother 45(4):999–1007

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Mah TF, O’Toole GA (2001) Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol 9(1):34–39

    CAS  PubMed  Google Scholar 

  13. Xu KD, McFeters GA, Stewart PS (2000) Biofilm resistance to antimicrobial agents. Microbiology 146(Pt 3):547–549

    CAS  PubMed  Google Scholar 

  14. Walters MC 3rd et al (2003) Contributions of antibiotic penetration, oxygen limitation, and low metabolic activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and tobramycin. Antimicrob Agents Chemother 47(1):317–323

    CAS  PubMed Central  PubMed  Google Scholar 

  15. Roberts AP, Mullany P (2006) Genetic basis of horizontal gene transfer among oral bacteria. Periodontol 2000 42:36–46

    PubMed  Google Scholar 

  16. Baehni PC, Takeuchi Y (2003) Anti-plaque agents in the prevention of biofilm-associated oral diseases. Oral Dis 9(Suppl 1):23–29

    PubMed  Google Scholar 

  17. van der Ouderaa FJ (1991) Anti-plaque agents. Rationale and prospects for prevention of gingivitis and periodontal disease. J Clin Periodontol 18(6):447–454

    PubMed  Google Scholar 

  18. Stewart PS (2003) Diffusion in biofilms. J Bacteriol 185(5):1485–1491

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Smith AW (2005) Biofilms and antibiotic therapy: is there a role for combating bacterial resistance by the use of novel drug delivery systems? Adv Drug Deliv Rev 57(10):1539–1550

    CAS  PubMed  Google Scholar 

  20. Beyth N et al (2008) Surface antimicrobial activity and biocompatibility of incorporated polyethylenimine nanoparticles. Biomaterials 29(31):4157–4163

    CAS  PubMed  Google Scholar 

  21. Beyth N et al (2006) Antibacterial activity of dental composites containing quaternary ammonium polyethylenimine nanoparticles against Streptococcus mutans. Biomaterials 27(21):3995–4002

    CAS  PubMed  Google Scholar 

  22. Beyth N et al (2010) Polyethyleneimine nanoparticles incorporated into resin composite cause cell death and trigger biofilm stress in vivo. Proc Natl Acad Sci U S A 107(51):22038–22043

    CAS  PubMed Central  PubMed  Google Scholar 

  23. Nel AE et al (2009) Understanding biophysicochemical interactions at the nano-bio interface. Nat Mater 8(7):543–557

    CAS  PubMed  Google Scholar 

  24. Marinho VC et al (2003) Systematic review of controlled trials on the effectiveness of fluoride gels for the prevention of dental caries in children. J Dent Educ 67(4):448–458

    PubMed  Google Scholar 

  25. Featherstone JD (2000) The science and practice of caries prevention. J Am Dent Assoc 131(7):887–899

    CAS  PubMed  Google Scholar 

  26. Featherstone JD (1999) Prevention and reversal of dental caries: role of low level fluoride. Community Dent Oral Epidemiol 27(1):31–40

    CAS  PubMed  Google Scholar 

  27. Pessan JP et al (2008) Slow-release fluoride devices: a literature review. J Appl Oral Sci 16(4):238–246

    CAS  PubMed  Google Scholar 

  28. Featherstone JD (2006) Delivery challenges for fluoride, chlorhexidine and xylitol. BMC Oral Health 6(Suppl 1):S8

    PubMed Central  PubMed  Google Scholar 

  29. Reynolds EC (1998) Anticariogenic complexes of amorphous calcium phosphate stabilized by casein phosphopeptides: a review. Spec Care Dentist 18(1):8–16

    CAS  PubMed  Google Scholar 

  30. Reynolds EC (1987) The prevention of sub-surface demineralization of bovine enamel and change in plaque composition by casein in an intra-oral model. J Dent Res 66(6):1120–1127

    CAS  PubMed  Google Scholar 

  31. Rao SK et al (2009) Study of the efficacy of toothpaste containing casein phosphopeptide in the prevention of dental caries: a randomized controlled trial in 12- to 15-year-old high caries risk children in Bangalore, India. Caries Res 43(6):430–435

    CAS  PubMed  Google Scholar 

  32. Bailey DL et al (2009) Regression of post-orthodontic lesions by a remineralizing cream. J Dent Res 88(12):1148–1153

    CAS  PubMed  Google Scholar 

  33. Morgan MV et al (2008) The anticariogenic effect of sugar-free gum containing CPP-ACP nanocomplexes on approximal caries determined using digital bitewing radiography. Caries Res 42(3):171–184

    CAS  PubMed  Google Scholar 

  34. Yengopal V, Mickenautsch S (2009) Caries preventive effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP): a meta-analysis. Acta Odontol Scand 67(6):321–332

    CAS  PubMed  Google Scholar 

  35. Cross KJ, Huq NL, Reynolds EC (2007) Casein phosphopeptides in oral health–chemistry and clinical applications. Curr Pharm Des 13(8):793–800

    CAS  PubMed  Google Scholar 

  36. Anderson MH (2003) A review of the efficacy of chlorhexidine on dental caries and the caries infection. J Calif Dent Assoc 31(3):211–214

    PubMed  Google Scholar 

  37. Jordan HV, De Paola PF (1974) Effect of a topically applied 3 percent vancomycin gel on Streptococcus mutans on different tooth surfaces. J Dent Res 53(1):115–120

    CAS  PubMed  Google Scholar 

  38. Zander HA, Bibby BG (1947) Laboratory and animal studies on the effect of penicillin on caries activity. J Dent Res 26(6):454

    CAS  PubMed  Google Scholar 

  39. Walker C (1990) Effects of sanguinarine and Sanguinaria extract on the microbiota associated with the oral cavity. J Can Dent Assoc 56(7 Suppl):13–30

    CAS  PubMed  Google Scholar 

  40. Shapiro S, Giertsen E, Guggenheim B (2002) An in vitro oral biofilm model for comparing the efficacy of antimicrobial mouthrinses. Caries Res 36(2):93–100

    CAS  PubMed  Google Scholar 

  41. Autio-Gold J (2008) The role of chlorhexidine in caries prevention. Oper Dent 33(6):710–716

    PubMed  Google Scholar 

  42. van Rijkom HM, Truin GJ, Van’t Hof MA (1998) A meta-analysis of clinical studies on the caries-inhibiting effect of fluoride gel treatment. Caries Res 32(2):83–92

    PubMed  Google Scholar 

  43. Svatun B et al (1993) The effects of three silica dentifrices containing Triclosan on supragingival plaque and calculus formation and on gingivitis. Int Dent J 43(4 Suppl 1):441–452

    CAS  PubMed  Google Scholar 

  44. Panagakos FS et al (2005) Advanced oral antibacterial/anti-inflammatory technology: a comprehensive review of the clinical benefits of a triclosan/copolymer/fluoride dentifrice. J Clin Dent 16(Suppl):S1–S19

    PubMed  Google Scholar 

  45. Gaffar A, et al. (1990) Antiplaque effects of dentifrices containing triclosan/copolymer/NaF system versus triclosan dentifrices without the copolymer. Am J Dent 3 Spec No:S7–14

    Google Scholar 

  46. Nabi N, et al. (1989) In vitro and in vivo studies on triclosan/PVM/MA copolymer/NaF combination as an anti-plaque agent. Am J Dent 2 Spec No:197–206

    Google Scholar 

  47. Chen F et al (2009) Tooth-binding micelles for dental caries prevention. Antimicrob Agents Chemother 53(11):4898–4902

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Petti S, Scully C (2009) Polyphenols, oral health and disease: a review. J Dent 37(6):413–423

    CAS  PubMed  Google Scholar 

  49. Brighenti FL et al (2012) Effect of Psidium cattleianum leaf extract on enamel demineralisation and dental biofilm composition in situ. Arch Oral Biol 57(8):1034–1040

    PubMed  Google Scholar 

  50. Diamond G et al (2009) The roles of antimicrobial peptides in innate host defense. Curr Pharm Des 15(21):2377–2392

    CAS  PubMed Central  PubMed  Google Scholar 

  51. Rennie J et al (2005) Simple oligomers as antimicrobial peptide mimics. J Ind Microbiol Biotechnol 32(7):296–300

    CAS  PubMed  Google Scholar 

  52. Wang TT et al (2004) Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 173(5):2909–2912

    CAS  PubMed  Google Scholar 

  53. Beckloff N et al (2007) Activity of an antimicrobial peptide mimetic against planktonic and biofilm cultures of oral pathogens. Antimicrob Agents Chemother 51(11):4125–4132

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Li L et al (2010) Design and characterization of an acid-activated antimicrobial peptide. Chem Biol Drug Des 75(1):127–132

    CAS  PubMed Central  PubMed  Google Scholar 

  55. Russell MW et al (2004) A caries vaccine? the state of the science of immunization against dental caries. Caries Res 38(3):230–235

    CAS  PubMed  Google Scholar 

  56. Sun Y et al (2012) Flagellin-PAc fusion protein is a high-efficacy anti-caries mucosal vaccine. J Dent Res 91(10):941–947

    CAS  PubMed  Google Scholar 

  57. Smith DJ, Mattos-Graner RO (2008) Secretory immunity following mutans streptococcal infection or immunization. Curr Top Microbiol Immunol 319:131–156

    CAS  PubMed  Google Scholar 

  58. Ma JK et al (1998) Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans. Nat Med 4(5):601–606

    CAS  PubMed  Google Scholar 

  59. Meurman JH (2005) Probiotics: do they have a role in oral medicine and dentistry? Eur J Oral Sci 113(3):188–196

    PubMed  Google Scholar 

  60. Milgrom P et al (2006) Mutans streptococci dose response to xylitol chewing gum. J Dent Res 85(2):177–181

    CAS  PubMed Central  PubMed  Google Scholar 

  61. Eke PI et al (2012) Prevalence of periodontitis in adults in the United States: 2009 and 2010. J Dent Res 91(10):914–920

    CAS  PubMed  Google Scholar 

  62. Paper I (1999) The pathogenesis of periodontal diseases. J Periodontol 70(4):457–470

    Google Scholar 

  63. Lang NP, Berglundh T (2011) Periimplant diseases: where are we now?–Consensus of the Seventh European Workshop on Periodontology. J Clin Periodontol 38(Suppl 11):178–181

    PubMed  Google Scholar 

  64. Cionca N et al (2010) Microbiologic testing and outcomes of full-mouth scaling and root planing with or without amoxicillin/metronidazole in chronic periodontitis. J Periodontol 81(1):15–23

    CAS  PubMed  Google Scholar 

  65. Pavicic MJ et al (1994) Microbiological and clinical effects of metronidazole and amoxicillin in Actinobacillus actinomycetemcomitans-associated periodontitis. A 2-year evaluation. J Clin Periodontol 21(2):107–112

    CAS  PubMed  Google Scholar 

  66. Davies RM, Ellwood RP, Davies GM (2004) The effectiveness of a toothpaste containing triclosan and polyvinyl-methyl ether maleic acid copolymer in improving plaque control and gingival health: a systematic review. J Clin Periodontol 31(12):1029–1033

    CAS  PubMed  Google Scholar 

  67. Rosling B et al (1997) The use of a triclosan/copolymer dentifrice may retard the progression of periodontitis. J Clin Periodontol 24(12):873–880

    CAS  PubMed  Google Scholar 

  68. Ellwood RP et al (1998) Effect of a triclosan/copolymer dentifrice on the incidence of periodontal attachment loss in adolescents. J Clin Periodontol 25(5):363–367

    CAS  PubMed  Google Scholar 

  69. Cullinan MP et al (2003) The effect of a triclosan-containing dentifrice on the progression of periodontal disease in an adult population. J Clin Periodontol 30(5):414–419

    CAS  PubMed  Google Scholar 

  70. Javed F, Al-Hezaimi K, Romanos GE (2012) Role of dentifrices with essential oil formulations in periodontal healing. Am J Med Sci 343(5):411–417

    PubMed  Google Scholar 

  71. Fornell J, Sundin Y, Lindhe J (1975) Effect of listerine on dental plaque and gingivitis. Scand J Dent Res 83(1):18–25

    CAS  PubMed  Google Scholar 

  72. DePaola LG et al (1989) Chemotherapeutic inhibition of supragingival dental plaque and gingivitis development. J Clin Periodontol 16(5):311–315

    CAS  PubMed  Google Scholar 

  73. Gordon JM, Lamster IB, Seiger MC (1985) Efficacy of Listerine antiseptic in inhibiting the development of plaque and gingivitis. J Clin Periodontol 12(8):697–704

    CAS  PubMed  Google Scholar 

  74. Loe H, Schiott CR (1970) The effect of mouthrinses and topical application of chlorhexidine on the development of dental plaque and gingivitis in man. J Periodontal Res 5(2):79–83

    CAS  PubMed  Google Scholar 

  75. Flotra L et al (1972) A 4-month study on the effect of chlorhexidine mouth washes on 50 soldiers. Scand J Dent Res 80(1):10–17

    CAS  PubMed  Google Scholar 

  76. Gunsolley JC (2010) Clinical efficacy of antimicrobial mouthrinses. J Dent 38(Suppl 1):S6–S10

    CAS  PubMed  Google Scholar 

  77. Overholser CD et al (1990) Comparative effects of 2 chemotherapeutic mouthrinses on the development of supragingival dental plaque and gingivitis. J Clin Periodontol 17(8):575–579

    CAS  PubMed  Google Scholar 

  78. Pires JR, Rossa Junior C, Pizzolitto AC (2007) In vitro antimicrobial efficiency of a mouthwash containing triclosan/gantrez and sodium bicarbonate. Braz Oral Res 21(4):342–347

    PubMed  Google Scholar 

  79. Gusberti FA et al (1988) Microbiological and clinical effects of chlorhexidine digluconate and hydrogen peroxide mouthrinses on developing plaque and gingivitis. J Clin Periodontol 15(1):60–67

    CAS  PubMed  Google Scholar 

  80. Weitzman SA et al (1984) Chronic treatment with hydrogen peroxide. Is it safe? J Periodontol 55(9):510–511

    CAS  PubMed  Google Scholar 

  81. Brecx M et al (1992) Efficacy of listerine, meridol and chlorhexidine mouthrinses as supplements to regular tooth cleaning measures. J Clin Periodontol 19(3):202–207

    CAS  PubMed  Google Scholar 

  82. Kalsi R, Vandana KL, Prakash S (2011) Effect of local drug delivery in chronic periodontitis patients: a meta-analysis. J Indian Soc Periodontol 15(4):304–309

    PubMed Central  PubMed  Google Scholar 

  83. Renvert S et al (2009) Mechanical non-surgical treatment of peri-implantitis: a double-blind randomized longitudinal clinical study. I: clinical results. J Clin Periodontol 36(7):604–609

    PubMed  Google Scholar 

  84. Karring ES et al (2005) Treatment of peri-implantitis by the Vector® system: a pilot study. Clin Oral Implants Res 16(3):288–293

    PubMed  Google Scholar 

  85. Mombelli A et al (2001) Treatment of peri-implantitis by local delivery of tetracycline: clinical, microbiological and radiological results. Clin Oral Implants Res 12(4):287–294

    CAS  PubMed  Google Scholar 

  86. Büchter A et al (2004) Sustained release of doxycycline for the treatment of peri-implantitis: randomised controlled trial. Br J Oral Maxillofac Surg 42(5):439–444

    PubMed  Google Scholar 

  87. Renvert S et al (2004) Treatment of incipient peri-implant infections using topical minocycline microspheres versus topical chlorhexidine gel as an adjunct to mechanical debridement. J Int Acad Periodontol 6(4 Suppl):154–159

    PubMed  Google Scholar 

  88. Peters OA et al (2001) Changes in root canal geometry after preparation assessed by high-resolution computed tomography. J Endod 27(1):1–6

    CAS  PubMed  Google Scholar 

  89. Gomes BPFA et al (2001) In vitro antimicrobial activity of several concentrations of sodium hypochlorite and chlorhexidine gluconate in the elimination of Enterococcus faecalis. Int Endod J 34(6):424–428

    CAS  PubMed  Google Scholar 

  90. Ferraz CCR et al (2001) In vitro assessment of the antimicrobial action and the mechanical ability of chlorhexidine gel as an endodontic irrigant. J Endod 27(7):452–455

    CAS  PubMed  Google Scholar 

  91. Zamany A, Safavi K, Spångberg LSW (2003) The effect of chlorhexidine as an endodontic disinfectant. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 96(5):578–581

    PubMed  Google Scholar 

  92. Siqueira JF Jr et al (2003) Elimination of Candida albicans infection of the radicular dentin by intracanal medications. J Endod 29(8):501–504

    PubMed  Google Scholar 

  93. Messer HH, Chen R-S (1984) The duration of effectiveness of root canal medicaments. J Endod 10(6):240–245

    CAS  PubMed  Google Scholar 

  94. Byström A, Claesson R, Sundqvist G (1985) The antibacterial effect of camphorated paramonochlorophenol, camphorated phenol and calcium hydroxide in the treatment of infected root canals. Dent Traumatol 1(5):170–175

    Google Scholar 

  95. Athanassiadis B, Abbott PV, Walsh LJ (2007) The use of calcium hydroxide, antibiotics and biocides as antimicrobial medicaments in endodontics. Aust Dent J 52:S64–S82

    CAS  PubMed  Google Scholar 

  96. Almyroudi A et al (2002) The effectiveness of various disinfectants used as endodontic intracanal medications: an in vitro study. J Endod 28(3):163–167

    PubMed  Google Scholar 

  97. Gomes BPFA et al (2003) Effectiveness of 2% chlorhexidine gel and calcium hydroxide against Enterococcus faecalis in bovine root dentine in vitro. Int Endod J 36(4):267–275

    CAS  PubMed  Google Scholar 

  98. Schäfer E, Bössmann K (2005) Antimicrobial efficacy of chlorhexidine and two calcium hydroxide formulations against enterococcus faecalis. J Endod 31(1):53–56

    PubMed  Google Scholar 

  99. Stabholz A et al (1993) Retention of antimicrobial activity by human root surfaces after in situ subgingival irrigation with tetracycline HCl or chlorhexidine. J Periodontol 64(2):137–141

    CAS  PubMed  Google Scholar 

  100. Khademi AA, Mohammadi Z, Havaee A (2006) Evaluation of the antibacterial substantivity of several intra-canal agents. Aust Endod J 32(3):112–115

    PubMed  Google Scholar 

  101. Rosenthal S, Spångberg L, Safavi K (2004) Chlorhexidine substantivity in root canal dentin. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 98(4):488–492

    PubMed  Google Scholar 

  102. Torabinejad M et al (2003) A new solution for the removal of the smear layer. J Endod 29(3):170–175

    PubMed  Google Scholar 

  103. Shabahang S, Torabinejad M (2003) Effect of MTAD on Enterococcus faecalis–contaminated root canals of extracted human teeth. J Endod 29(9):576–579

    PubMed  Google Scholar 

  104. Shabahang S, Pouresmail M, Torabinejad M (2003) In vitro antimicrobial efficacy of MTAD and sodium hypochlorite. J Endod 29(7):450–452

    PubMed  Google Scholar 

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Beyth, N., Haramaty, O., Polak, D. (2014). Focal Drug Delivery for Management of Oral Infections. In: Domb, A., Khan, W. (eds) Focal Controlled Drug Delivery. Advances in Delivery Science and Technology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-9434-8_14

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