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The Development of Drug-Free Therapy for Prevention of Dental Caries

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ABSTRACT

Purpose

The purpose of this study was to develop a novel, drug-free therapy that can reduce the over-accumulation of cariogenic bacteria on dental surfaces.

Methods

We designed and synthesized a polyethylene glycol (PEG)-based hydrophilic copolymer functionalized with a pyrophosphate (PPi) tooth-binding anchor using “click” chemistry. The polymer was then evaluated for hydroxyapatite (HA) binding kinetics and capability of reducing bacteria adhesion to artificial tooth surface.

Results

The PPi-PEG copolymer can effectively inhibit salivary protein adsorption after rapid binding to an artificial tooth surface. As a result, the in vitro S. mutans adhesion study showed that the PPi-PEG copolymer can inhibit saliva protein-promoted S. mutans adhesion through the creation of a neutral, hydrophilic layer on the artificial tooth surface.

Conclusions

The results suggested the potential application of a PPi-PEG copolymer as a drug-free alternative to current antimicrobial therapy for caries prevention.

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Abbreviations

CFU:

Colony forming units

Click-PEG:

Multifunctional polyethylene glycol copolymer synthesized using click chemistry

DCC:

N,N’-dicyclohexylcarbodiimide

DCM:

Dichloromethane

DMAP:

4-dimethylaminopyridine

DMF:

Dimethylformamide

EDTA:

Ethylenediaminetetraacetic acid

GRAS:

Generally regarded as safe

HA:

Hydroxyapatite

HMHP:

PPi-PEG copolymer with high MW and high pyrophosphate content

HMLP:

PPi-PEG copolymer with high MW and low pyrophosphate content

IRB:

Institutional review board

LMHP:

PPi-PEG copolymer with low MW and high pyrophosphate content

LMLP:

PPi-PEG copolymer with low MW and low pyrophosphate content

MW:

Molecular weight

PDI:

Polydispersity index

PEG:

Polyethylene glycol

PPi:

Pyrophosphate

PPi-PEG:

Pyrophosphate modified click-PEG

S. mutans :

Streptococcus mutans

TBAP:

Tris(tetra-n-butylammonium) hydrogen pyrophosphate

THYE:

Todd Hewitt-yeast extract

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was supported in part by NIH grants R03 DE019179 (KCR), R01 AI038901 (KWB) and Nebraska Research Initiative (NRI) Proof-of-Concept Award (DW). FC also acknowledges the graduate fellowship support from University of Nebraska Medical Center. The authors of this article declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 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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Corresponding author

Correspondence to Dong Wang.

Additional information

Fu Chen and Zhenshan Jia contributed equally to this manuscript.

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Chen, F., Jia, Z., Rice, K.C. et al. The Development of Drug-Free Therapy for Prevention of Dental Caries. Pharm Res 31, 3031–3037 (2014). https://doi.org/10.1007/s11095-014-1396-1

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  • DOI: https://doi.org/10.1007/s11095-014-1396-1

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