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Pharmaceutical Research

, Volume 30, Issue 11, pp 2808–2817 | Cite as

The Development of Dentotropic Micelles with Biodegradable Tooth-Binding Moieties

  • Fu Chen
  • Zhenshan Jia
  • Kelly C. Rice
  • Richard A. Reinhardt
  • Kenneth W. Bayles
  • Dong Wang
Research Paper

ABSTRACT

Purpose

Development of dentotropic (tooth-binding) micelle formulations to improved efficacy and safety of antimicrobial therapy for dental plaque prevention and treatment.

Methods

Because of their excellent biocompatibility and biodegradability, diphosphoserine peptide and pyrophosphate were selected as the tooth-binding moieties to replace alendronate, which was used previously. Diphosphoserine peptide was conjugated to Pluronic P123 using “click” chemistry, whereas pyrophosphate was attached to P123 through an ester bond. The tooth-binding micelles (TBMs) were prepared by self-assembly of the modified P123 with the antimicrobial agent triclosan. The influence of human saliva and/or its components on TBMs’ drug-releasing profile, tooth-binding potential and binding stability was evaluated in vitro. S. mutans UA159 biofilm formed on hydroxyapatite (HA) discs was used to evaluate the TBMs’ therapeutic potential.

Results

Saliva does not affect triclosan release from TBMs. More than 60% of TBMs’ HA binding capacity was maintained in the presence of saliva. Less than 5% of TBMs bound to HA was released over 24 h in human saliva, protease or phosphatase, suggesting the retention properties of the TBMs will not be compromised due to the biodegradable nature of the binding moieties. In both in vitro biofilm prevention and treatment studies, the TBM treated group showed significantly lower CFU per HA disc compared to the controls (2-log reduction, p < 0.05).

Conclusion

The data from these studies suggest that the novel dentotropic micelle formulations bearing biodegradable tooth-binding moieties can be used as an effective and safe delivery tool for antimicrobials to improve dental plaque prevention and treatment.

KEY WORDS

antimicrobial biofilm dental plaque dentotropic Pluronic micelle 

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

This work was supported in part by NIH grants R03 DE019179 (KCR), R01 AI038901, P01 AI083211 (KWB) and Nebraska Research Initiative (NRI) Proof-of-Concept Award (DW). DW is one of the inventors of the dentotropic micelle technology, which has been filed for PCT patent application.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Fu Chen
    • 1
  • Zhenshan Jia
    • 1
  • Kelly C. Rice
    • 4
  • Richard A. Reinhardt
    • 2
  • Kenneth W. Bayles
    • 3
  • Dong Wang
    • 1
  1. 1.Department of Pharmaceutical Sciences, College of PharmacyUniversity of Nebraska Medical CenterOmahaUSA
  2. 2.Department of Surgical Specialties, College of DentistryUniversity of Nebraska Medical CenterLincolnUSA
  3. 3.Department of Pathology and MicrobiologyUniversity of Nebraska Medical CenterOmahaUSA
  4. 4.Department of Microbiology and Cell ScienceUniversity of FloridaGainesvilleUSA

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