Skip to main content

Advertisement

Log in

Triclosan-Loaded Tooth-Binding Micelles for Prevention and Treatment of Dental Biofilm

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

ABSTRACT

Purpose

To develop tooth-binding micelle formulations of triclosan for the prevention and treatment of dental caries.

Methods

Alendronate (ALN) was conjugated to the chain termini of different Pluronic copolymers to confer tooth-binding ability to the micelles. Using 3 different formulation methods, Pluronics and ALN-modified Pluronics were used to prepare triclosan-loaded tooth-binding micelles. The formulation parameters were optimized for triclosan solubility, particle size, hydroxyapatite (HA) binding capability and in vitro drug release profile. The optimized formulation was tested on an in vitro biofilm model.

Results

Direct dissolution was selected as the best formulation method. Triclosan-loaded tooth-binding micelles were able to inhibit initial biofilm growth of Streptococcus mutans UA159 by 6-log CFU/HA disc compared to the untreated control. These tooth-binding micelles were also able to reduce the viability of preformed biofilm by 4-log CFU/HA disc compared to the untreated control.

Conclusions

Triclosan-loaded tooth-binding micelle formulations have been successfully developed and optimized in this study. These micelle formulations demonstrated promising anti-cariogenic bacteria capabilities and may find applications in the prevention and treatment of dental caries.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

REFERENCES

  1. Senadheera D, Cvitkovitch DG. Quorum sensing and biofilm formation by Streptococcus mutans. Adv Exp Med Biol. 2008;631:178–88.

    Article  PubMed  Google Scholar 

  2. Keyes PH. The infectious and transmissible nature of experimental dental caries. Findings and implications. Arch Oral Biol. 1960;1:304–20.

    Article  CAS  PubMed  Google Scholar 

  3. Loesche WJ. Role of Streptococcus mutans in human dental decay. Microbiol Rev. 1986;50:353–80.

    CAS  PubMed  Google Scholar 

  4. Kuramitsu HK. Virulence factors of mutans streptococci: role of molecular genetics. Crit Rev Oral Biol Med. 1993;4:159–76.

    CAS  PubMed  Google Scholar 

  5. Kuramitsu HK. Virulence properties of oral bacteria: impact of molecular biology. Curr Issues Mol Biol. 2001;3:35–6.

    CAS  PubMed  Google Scholar 

  6. Bowden GH, Hamilton IR. Survival of oral bacteria. Crit Rev Oral Biol Med. 1998;9:54–85.

    Article  CAS  PubMed  Google Scholar 

  7. Marsh PD, Bradshaw DJ. Dental plaque as a biofilm. J Ind Microbiol. 1995;15:169–75.

    Article  CAS  PubMed  Google Scholar 

  8. Gilbert P, Das J, Foley I. Biofilm susceptibility to antimicrobials. Adv Dent Res. 1997;11:160–7.

    Article  CAS  PubMed  Google Scholar 

  9. Ceri H, Olson ME, Stremick C, Read RR, Morck D, Buret A. The Calgary Biofilm Device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. J Clin Microbiol. 1999;37:1771–6.

    CAS  PubMed  Google Scholar 

  10. van der Ouderaaand F, Cummins D. Delivery systems for agents in supra- and sub-gingival plaque control. J Dent Res. 1989;68:1617–24.

    Google Scholar 

  11. Furiaand TE, Schenkel AG. A new, broad spectrum bacteriostat. Soap Chem Spec. 1968;44:47–50. 116–22.

    Google Scholar 

  12. Food and Drug Administration, FDA approves first toothpaste for gum disease, FDA Talk paper, July 14th (1997). FDA Talk paper.

  13. Raghavan SL, Schuessel K, Davis A, Hadgraft J. Formation and stabilisation of triclosan colloidal suspensions using supersaturated systems. Int J Pharm. 2003;261:153–8.

    Article  CAS  PubMed  Google Scholar 

  14. Gilbert RJ, Williams PE. The oral retention and antiplaque efficacy of triclosan in human volunteers. Br J Clin Pharmacol. 1987;23:579–83.

    CAS  PubMed  Google Scholar 

  15. Phan TN, Marquis RE. Triclosan inhibition of membrane enzymes and glycolysis of Streptococcus mutans in suspensions and biofilms. Can J Microbiol. 2006;52:977–83.

    Article  CAS  PubMed  Google Scholar 

  16. Bradshaw DJ, Marsh PD, Watson GK, Cummins D. The effects of triclosan and zinc citrate, alone and in combination, on a community of oral bacteria grown in vitro. J Dent Res. 1993;72:25–30.

    CAS  PubMed  Google Scholar 

  17. Chen F, Liu XM, Rice KC, Li X, Yu F, Reinhardt RA et al. Tooth-binding micelles for dental caries prevention. Antimicrob Agents Chemother. 2009;53:4898–902.

    Article  CAS  PubMed  Google Scholar 

  18. Murchison HH, Barrett JF, Cardineau GA, Curtiss 3rd R. Transformation of Streptococcus mutans with chromosomal and shuttle plasmid (pYA629) DNAs. Infect Immun. 1986;54:273–82.

    CAS  PubMed  Google Scholar 

  19. Biswas I, Drake L, Biswas S. Regulation of gbpC expression in Streptococcus mutans. J Bacteriol. 2007;189:6521–31.

    Article  CAS  PubMed  Google Scholar 

  20. Jett BD, Hatter KL, Huycke MM, Gilmore MS. Simplified agar plate method for quantifying viable bacteria. Biotechniques. 1997;23:648–50.

    CAS  PubMed  Google Scholar 

  21. Wei Z, Hao J, Yuan S, Li Y, Juan W, Sha X et al. Paclitaxel-loaded Pluronic P123/F127 mixed polymeric micelles: formulation, optimization and in vitro characterization. Int J Pharm. 2009;376:176–85.

    Article  CAS  PubMed  Google Scholar 

  22. Blanco E, Bey EA, Dong Y, Weinberg BD, Sutton DM, Boothman DA et al. Beta-lapachone-containing PEG-PLA polymer micelles as novel nanotherapeutics against NQO1-overexpressing tumor cells. J Control Release. 2007;122:365–74.

    Article  CAS  PubMed  Google Scholar 

  23. Chiappetta DA, Degrossi J, Teves S, D’Aquino M, Bregni C, Sosnik A. Triclosan-loaded poloxamine micelles for enhanced topical antibacterial activity against biofilm. Eur J Pharm Biopharm. 2008;69:535–45.

    Article  CAS  PubMed  Google Scholar 

  24. Shinoda H, Adamek G, Felix R, Fleisch H, Schenk R, Hagan P. Structure-activity relationships of various bisphosphonates. Calcif Tissue Int. 1983;35:87–99.

    Article  CAS  PubMed  Google Scholar 

  25. Fujisawa R, Wada Y, Nodasaka Y, Kuboki Y. Acidic amino acid-rich sequences as binding sites of osteonectin to hydroxyapatite crystals. Biochim Biophys Acta. 1996;1292:53–60.

    PubMed  Google Scholar 

  26. Yang L, Wu X, Liu F, Duan Y, Li S. Novel biodegradable polylactide/poly(ethylene glycol) micelles prepared by direct dissolution method for controlled delivery of anticancer drugs. Pharm Res. 2009;26:2332–42.

    Article  CAS  PubMed  Google Scholar 

  27. Oh KT, Bronich TK, Kabanov AV. Micellar formulations for drug delivery based on mixtures of hydrophobic and hydrophilic Pluronic block copolymers. J Control Release. 2004;94:411–22.

    Article  CAS  PubMed  Google Scholar 

  28. R. Nagarajan. Solubilization of hydrocarbons and resulting aggregate shape transitions in aqueous solutions of Pluronic® (PEO–PPO–PEO) block copolymers. Coll. Surf. B: Biointerf. 1999; 55–72.

  29. Xu RL, Winnik MA, Hallett FR, Riess G, Croucher MD. Light-scattering study of the association behavior of styrene-ethylene oxide block copolymers in aqueous solution. Macromolecules. 1991;24:87–93.

    Article  CAS  Google Scholar 

  30. Chu B, Zhou Z. Nonionic Surfactants: polyoxyalkylene block copolymers. New York: Marcel Dekker, Inc.; 1996.

    Google Scholar 

  31. Kabanov AV, Alakhov VY. Pluronic block copolymers in drug delivery: from micellar nanocontainers to biological response modifiers. Crit Rev Ther Drug Carrier Syst. 2002;19:1–72.

    Article  CAS  PubMed  Google Scholar 

  32. Croy SR, Kwon GS. Polymeric micelles for drug delivery. Curr Pharm Des. 2006;12:4669–84.

    Article  CAS  PubMed  Google Scholar 

  33. Kozlov MY, Melik-Nubarov NS, Batrakova EV, Kabanov AV. Relationship between Pluronic Block Copolymer Structure. Critical Micellization Concentration and Partitioning Coefficients of Low Molecular Mass Solutes. Macromolecules. 2000;33:3305–13.

    Article  CAS  Google Scholar 

  34. Sjogren K, Lundberg AB, Birkhed D, Dudgeon DJ, Johnson MR. Interproximal plaque mass and fluoride retention after brushing and flossing–a comparative study of powered toothbrushing, manual toothbrushing and flossing. Oral Health Prev Dent. 2004;2:119–24.

    PubMed  Google Scholar 

Download references

ACKNOWLEDGMENT

This work was supported in part by NIH grants R03 DE019179 (KCR), R01 AI038901 (KWB) and R01 AR053325 (DW). We also acknowledge partial support of NIH COBRE grant RR021937 (Nebraska Center for Nanomedicine).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Kenneth W. Bayles or Dong Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, F., Rice, K.C., Liu, XM. et al. Triclosan-Loaded Tooth-Binding Micelles for Prevention and Treatment of Dental Biofilm. Pharm Res 27, 2356–2364 (2010). https://doi.org/10.1007/s11095-010-0119-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-010-0119-5

KEY WORDS

Navigation