Tooth-binding micelles for dental caries prevention.
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.
Chen
Fu
F
Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198-6025, USA.
Liu
Xin-Ming
XM
Rice
Kelly C
KC
Li
Xue
X
Yu
Fang
F
Reinhardt
Richard A
RA
Bayles
Kenneth W
KW
Wang
Dong
D
D018441:Biofilms; D003731:Dental Caries / Q000517:prevention & control*; D016503:Drug Delivery Systems; D017886:Durapatite / Q000378:metabolism; D005204:Farnesol / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D008823:Micelles; D013295:Streptococcus mutans / Q000187:drug effects / Q000254:growth & development; D014070:Tooth / Q000378:metabolism*
D008823:Micelles; D005204:Farnesol; D017886:Durapatite
J Calif Dent Assoc. 2003 Mar;31(3):257-69
12693825
Adv Drug Deliv Rev. 2005 May 25;57(7):1049-76
15876403
Adv Drug Deliv Rev. 2002 Feb 21;54(2):223-33
11897147
Pediatrics. 2007 Mar;119 Suppl 2:S150-62
17332236
J Bacteriol. 2007 Sep;189(18):6521-31
17616585
Antimicrob Agents Chemother. 2002 May;46(5):1302-9
11959560
J Drug Target. 2006 Sep;14(8):583-97
17050124
BMC Oral Health. 2006 Jun 15;6 Suppl 1:S8
16934125
Infect Immun. 1986 Nov;54(2):273-82
3021626
Lancet. 2007 Jan 6;369(9555):51-9
17208642
J Clin Dent. 2007;18(3):79-81
17913001
J Am Dent Assoc. 2008 Dec;139(12):1674-7
19047674
J West Soc Periodontol Periodontal Abstr. 2002;50(1):5-9
12049062
Int J Pharm. 2000 Jan 5;193(2):197-203
10606782
Acta Pharm. 2003 Sep;53(3):199-212
14769243
J Pharm Sci. 1999 Jun;88(6):592-8
10350494
J Clin Periodontol. 2002 Jan;29(1):1-8
11846842
J Control Release. 2007 Sep 11;122(1):54-62
17673326
Braz Dent J. 2001;12(3):209-13
11696921
Int J Pharm. 2002 May 15;238(1-2):93-103
11996813
Biotechniques. 1997 Oct;23(4):648-50
9343684
Oral Microbiol Immunol. 2002 Dec;17(6):337-43
12485324
Appl Environ Microbiol. 2001 Jul;67(7):2982-92
11425711
Eur J Pharm Biopharm. 2002 Mar;53(2):233-9
11880008
J Dent Res. 2005 Nov;84(11):1016-20
16246933
Oper Dent. 2008 Mar-Apr;33(2):142-8
18435187
J Control Release. 2006 Aug 10;114(1):15-40
16828915
J Am Dent Assoc. 2000 Jul;131(7):887-99
10916327
Int J Biol Macromol. 2006 Dec 15;40(1):9-14
16837041
Boll Chim Farm. 1997 Jul-Aug;136(7):543-8
9432193