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The Development of Dentotropic Micelles with Biodegradable Tooth-Binding Moieties

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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.

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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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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, 68198-6025, USA

    Fu Chen, Zhenshan Jia & Dong Wang

  2. Department of Surgical Specialties, College of Dentistry, University of Nebraska Medical Center, Lincoln, Nebraska, 68583-0740, USA

    Richard A. Reinhardt

  3. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, 68198-6025, USA

    Kenneth W. Bayles

  4. Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida, 32611-0700, USA

    Kelly C. Rice

Authors
  1. Fu Chen
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  2. Zhenshan Jia
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  3. Kelly C. Rice
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  4. Richard A. Reinhardt
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  5. Kenneth W. Bayles
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  6. Dong Wang
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Correspondence to Dong Wang.

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Chen, F., Jia, Z., Rice, K.C. et al. The Development of Dentotropic Micelles with Biodegradable Tooth-Binding Moieties. Pharm Res 30, 2808–2817 (2013). https://doi.org/10.1007/s11095-013-1105-5

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  • DOI: https://doi.org/10.1007/s11095-013-1105-5

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