Skip to main content

Advertisement

SpringerLink
Log in

Development of a peptide-containing chewing gum as a sustained release antiplaque antimicrobial delivery system

  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The objective of this study was to characterize the stability of KSL-W, an antimicrobial decapeptide shown to inhibit the growth of oral bacterial strains associated with caries development and plaque formation, and its potential as an antiplaque agent in a chewing gum formulation. KSL-W formulations with or without the commercial antibacterial agent cetylpyridinium chloride (CPC) were prepared. The release of KSL-W from the gums was assessed in vitro using a chewing gum apparatus and in vivo by a chew-out method. A reverse-phase high-performance liquid chromatography method was developed for assaying KSL-W. Raw material stability and temperature and pH effects on the stability of KSL-W solutions and interactions of KSL-W with tooth-like material, hydroxyapatite discs, were investigated.

KSL-W was most stable in acidic aqueous solutions and underwent rapid hydrolysis in base. It was stable to enzymatic degradation in human saliva for 1 hour but was degraded by pancreatic serine proteases. KSL-W readily adsorbed to hydroxyapatite, suggesting that it will also adsorb to the teeth when delivered to the oral cavity. The inclusion of CPC caused a large increase in the rate and extent of KSL-W released from the gums. The gum formulations displayed promising in vitro/ in vivo release profiles, wherein as much as 90% of the KSL-W was released in a sustained manner within 30 minutes in vivo. These results suggest that KSL-W possesses the stability, adsorption, and release characteristics necessary for local delivery to the oral cavity in a chewing gum formulation, there-by serving as a novel antiplaque agent.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Paster BJ, Olsen I, Aas JA, Dewhirst FE. The breadth of bacterial diversity in the human periodontal pocket and other oral sites.Periodontol 2000. 2006;42:80–87.

    Article  Google Scholar 

  2. Aas JA, Paster BJ, Stokes LN, Olsen I, Dewhirst FE. Defining the normal bacterial oral cavity.J Clin Microbiol. 2005;43:5721–5732.

    Article  Google Scholar 

  3. Marsh PD. Dental plaque as a biofilm and a microbial community: implications for health and disease.BMC Oral Health. 2006;6:S14.

    Article  CAS  Google Scholar 

  4. Holt RL. Studies on human dental plaque. 1. Physical and chemical characteristics and enzyme activities of pooled plaque extracts.J Oral Pathol. 1975;4:73–85.

    Article  CAS  Google Scholar 

  5. Scheie AA, Fejerskov O, Danielsen B. The effects of xylitol-containing chewing gums on dental plaque and acidogenic potential.Int Dent J. 1994;46:91–96.

    Google Scholar 

  6. Papanaou PN. Microbial markers of periodontal diseases In: Busscher HJ, Evans LV, eds.Oral Biofilms and Plaque Controls. Amsterdam, The Netherlands: Harwood Academic Publishers: 1999:205–220.

    Google Scholar 

  7. Olsson J, van der Heijde Y, Holmberg K. Plaque formation in vivo and bacterial attachment in vitro on permanently hydrophobic and hydrophilic surfaces.Caries Res. 1992;26:428–433.

    Article  CAS  Google Scholar 

  8. Gibbons RJ. Bacterial adhesion to oral tissues: a model for infectious diseases.J Dent Res. 1989;68:750–760.

    CAS  Google Scholar 

  9. Marsh PD. Microbial ecology of dental plaque and its significance in health and disease.Adv Dent Res. 1994;8:263–271.

    CAS  Google Scholar 

  10. Concannon SP, Crowe TD, Abercrombie JJ, et al. Susceptibility of oral bacteria to an antimicrobial decapeptide.J Med Microbiol. 2003;52:1083–1093.

    Article  CAS  Google Scholar 

  11. Wilson M. Susceptibility of oral bacterial biofilms to antimicrobial agents.J Med Microbiol. 1996;44:79–87.

    Article  Google Scholar 

  12. Leung KP, Crowe TD, Abercrombie JJ, et al. Control of oral biofilm formation by an antimicrobial decapeptide.J Dent Res. 2005;84: 1172–1177.

    CAS  Google Scholar 

  13. Na DH, Faraj J, Capan Y, Leung KP, DeLuca PP. Chewing gum of antimicrobial decapeptide (KSL) as a sustained antiplaque agent: preformulation study.J Control Release. 2005;107:122–130.

    Article  CAS  Google Scholar 

  14. Na DH, Faraj J, Capan Y, Leung KP, DeLuca PP. Stability of antimicrobial decapeptide (KSL) and its analogues for delivery in the oral cavity.Pharm Res. In press.

  15. Bonesvoll P, Lokken P, Rolla G, Paus PN. Retention of chlorhexidine in the human oral cavity after mouth rinses.Arch Oral Biol. 1974;19:209–212.

    Article  CAS  Google Scholar 

  16. Ainamo J, Etemadzadeh H. Prevention of plaque growth with chewing gum containing chlorhexidine acetate.J Clin Periodontol. 1987;14:524–527.

    Article  CAS  Google Scholar 

  17. Rassing MR. Chewing gum as a drug delivery system.Adv Drug Deliv Rev. 1994;13:89–121.

    Article  CAS  Google Scholar 

  18. Jenssen ME, Lokind KB. Chewing gum as a drug delivery system: influence of additives upon the rate of release metronidazole and propranolol hydrochloride from chewing gum.Farm Sci Ed. 1988;16:94–97.

    Google Scholar 

  19. Yang X, Wang G, Zhang X. Release kinetics of catechines from chewing gum.J Pharm Sci. 2004;93:293–299.

    Article  CAS  Google Scholar 

  20. Krook M, Lindbladh C, Eriksen JA, Mosbach K. Selection of a cyclic nonapeptide inhibitor to α-chymotripsin using a phage display peptide library.Mol Divers. 1997;3:149–159.

    Article  CAS  Google Scholar 

  21. Kvist C, Andersson SB, Fors S, Wennergren B, Berglund J. Apparatus for studying in vitro drug release from medicated chewing gums.Int J Pharm. 1999;189:57–65.

    Article  CAS  Google Scholar 

  22. Rassing MR. Specialized oral mucosal drug delivery systems: chewing gums. In: Rathbone MJ, ed.Oral Mucosal Drug Delivery. New York, NY: Marcel Dekker; 1996:319–357.

    Google Scholar 

  23. Rolla G, Loe H, Schiott CR. Affinity of chlorhexidine to hydroxyapatite and to salivary mucins.J Periodontal Res. 1970;5:90–95.

    Article  CAS  Google Scholar 

  24. Rolla G, Loe H, Schiott CR. The retention of chlorhexidine in the human oral cavity.Arch Oral Biol. 1971;16:1109–1116.

    Article  CAS  Google Scholar 

  25. Emilson CG, Erickson T, Heyden G, Magnusson BC. Uptake of chlorhexidine to hydroxyapatite.J Periodontal Res. 1973;8:17–21.

    Article  Google Scholar 

  26. Charles CH, Mostler KM, Bartels LL, Mankodi SM. Comparative anti-plaque and antigingivitis effectiveness of a chlorhexidine and an essential oil mouth rinse: 6-month clinical trial.J Clin Periodontol. 2004;31:878–884.

    Article  CAS  Google Scholar 

  27. Ehara A, Torii M, Imazato S, Ebisu S. Antibacterial activities and release kinetics of a newly developed recoverable controlled agent-release system.J Dent Res. 2000;79:824–828.

    CAS  Google Scholar 

  28. Siewert M, Dressman J, Brown CK, Shah VP. FIP/AAPS guidelines to dissolution/in vitro release testing of novel/special dosage forms.AAPS PharmSciTech. 2003;4:Article 7.

  29. Lif Holgerson P, Stecksen-Blicks C, Sjostrom I, Twetman S. Effect of xylitol-containing chewing gums on interdental plaque: pH in habitual xylitol consumers.Acta Odontol Scand. 2005;63:233–238.

    Article  CAS  Google Scholar 

  30. Soderling E, Trahan L, Tammiala-Salonen T, Hakkinen L. Effect of xylitol, xylitol-sorbitol and placebo chewing gums on the plaque of habitual xylitol consumers.Eur J Oral Sci. 1997;105: 170–177.

    Article  CAS  Google Scholar 

  31. Humphrey SP, Williamson RT. A review of saliva: normal composition, flow, and function.J Prosthet Dent. 2001;85:162–169.

    Article  CAS  Google Scholar 

  32. Herrera D, Santos S, Ferrus J, Barbieri G, Trombelli L, Sanz M. Efficacy of a 0.15% benzydamine hydrochloride and 0.05% cetylpyridinium chloride mouth rinse on 4-day de novo plaque formation.J Clin Periodontol. 2005;32:595–603.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lexington, KY

    Jabar A. Faraj, David Worthen & Patrick P. DeLuca

  2. Department of Medicinal Chemistry, University of Pavia, Italy

    Rossella Dorati

  3. Department of Chemistry and Technology of Drugs, University of Perugia, Italy

    Aurélie Schoubben

  4. Institute of Medicinal Chemistry and Toxicology University of Milan, Italy

    Francesca Selmin

  5. Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100, Ankara, Turkey

    Yilmaz Capan

  6. Microbiology Branch, US Army Dental and Trauma Research Detachment, Walter Reed Army Institute of Research, Great Lakes, IL

    Kai Leung

Authors
  1. Jabar A. Faraj
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rossella Dorati
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aurélie Schoubben
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David Worthen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Francesca Selmin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yilmaz Capan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kai Leung
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Patrick P. DeLuca
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yilmaz Capan.

Additional information

Published: March 30, 2007

Rights and permissions

Reprints and permissions

About this article

Cite this article

Faraj, J.A., Dorati, R., Schoubben, A. et al. Development of a peptide-containing chewing gum as a sustained release antiplaque antimicrobial delivery system. AAPS PharmSciTech 8, 26 (2007). https://doi.org/10.1208/pt0801026

Download citation

  • Received:

  • Accepted:

  • DOI: https://doi.org/10.1208/pt0801026

Keywords

Search

Navigation