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Antimicrobial Agents and Chemotherapy, November 2009, p. 4898-4902, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00387-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Tooth-Binding Micelles for Dental Caries Prevention{triangledown}

Fu Chen,1,{dagger} Xin-Ming Liu,1,{dagger} Kelly C. Rice,2,5 Xue Li,1 Fang Yu,3 Richard A. Reinhardt,4 Kenneth W. Bayles,2* and Dong Wang1*

Department of Pharmaceutical Sciences, College of Pharmacy,1 Department of Pathology and Microbiology,2 Department of Biostatistics, College of Public Health,3 Department of Surgical Specialties, College of Dentistry, University of Nebraska Medical Center, Omaha, Nebraska 68198-6025,4 Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida 32611-07005

Received 23 March 2009/ Returned for modification 15 June 2009/ Accepted 18 August 2009

Maintenance of the effective local concentration of antimicrobials on the tooth surface is critical for the management of cariogenic bacteria in the oral cavity. We report on the design of a simple tooth-binding micellar drug delivery platform that would effectively bind to tooth surfaces. To achieve tooth-binding ability, the chain termini of biocompatible Pluronic copolymers were modified with a biomineral-binding moiety (i.e., alendronate). The micelles formulated with this polymer were shown to be able to swiftly (<1 min) bind to hydroxyapatite (HA; a model tooth surface) and gradually release the encapsulated model antimicrobial (farnesol). These tooth-binding micelles were negatively charged and had an average effective hydrodynamic diameter of less than 100 nm. In vitro biofilm inhibition studies demonstrated that the farnesol-containing tooth-binding micelles were able to provide significantly stronger inhibition of Streptococcus mutans UA159 biofilm formation on HA discs than the untreated blank control micelles (P < 0.0001). Upon further optimization, this delivery platform could provide an effective tool for caries prevention and treatment.

* Corresponding author. Mailing address for Dong Wang: Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198-6025. Phone: (402) 559-1995. Fax: (402) 559-9543. E-mail: dwang{at}unmc.edu. Mailing address for Kenneth W. Bayles: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-6025. Phone: (402) 559-4945. Fax: (402) 559-5900. E-mail: kbayles{at}unmc.edu

{triangledown} Published ahead of print on 24 August 2009.

{dagger} These individuals contributed equally to this work.

Antimicrobial Agents and Chemotherapy, November 2009, p. 4898-4902, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00387-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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