title: Development of a peptide-containing chewing gum as a sustained release antiplaque antimicrobial delivery system.
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, thereby serving as a novel antiplaque agent.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lexington, KY, USA.
authors.forename: Jabar A
authors.initials: JA
authors.lastname: Faraj
authors.forename: Rossella
authors.initials: R
authors.lastname: Dorati
authors.forename: Aurélie
authors.initials: A
authors.lastname: Schoubben
authors.forename: David
authors.initials: D
authors.lastname: Worthen
authors.forename: Francesca
authors.initials: F
authors.lastname: Selmin
authors.forename: Yilmaz
authors.initials: Y
authors.lastname: Capan
authors.forename: Kai
authors.initials: K
authors.lastname: Leung
authors.forename: Patrick P
authors.initials: PP
authors.lastname: DeLuca
mesh_terms: D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage* / Q000737:chemistry*; D002638:Chewing Gum; D003692:Delayed-Action Preparations / Q000737:chemistry*; D003773:Dental Plaque / Q000517:prevention & control*; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D004353:Drug Evaluation, Preclinical; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D008422:Materials Testing; D012463:Saliva / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002638:Chewing Gum; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients