Caries remains a major problem; most lesions occur in fissures of permanent molars. Xylitol is an effective tooth decay preventive. Xylitol exerts selective antibacterial-like actions against mutans streptococci (MS) because of its disruption of their energy metabolism and growth and reduces accumulation of MS in tooth biofilms. Both ADA and AAPD recommend xylitol. Yet while the greatest need is in the fissures, current vehicles are only partially effective. We think that for youngsters a thixotropic xylitol delivery system (THXX) designed to be mechanically a) self-deliverable to and b) retentive in tooth fissures of the molar and bicuspid teeth will have great utility. Properly formulated THXX systems, as a consequence of the shearing effects of mechanical stress, can be made to flow into tooth fissures aided by occlusion and be retained in mechanically sheltered tooth fissures, as a consequence of thixotropic re-solidification. We posit xylitol will be slowly eluted from THXX and bioavailable as a result of its concentration in fissures. Adequate time will exist for xylitolto exert its anti-mutans-growth influence because salivary laminar flow over fissures is so slow. The Specific Aims are to: 1. Develop a thixotropic-xylitol-containing delivery system (THXX) that targets caries prevention in fissures. We shall demonstrate THXX is mechanically forced by chewing into posterior tooth fissures, and retained in those sheltered locations due to thixotropic re-solidification after the mechanical shear forces of chewing have been discontinued. We shall use posterior tooth fissures of articulated extracted teeth for this demonstration. To formulate THXX with optimal retention, we shall use a food dye-containing THXX, using quantitative analyses of dye recovery from THXX lodged in fissures as a surrogate for delivery and retention of the THXX.; 2. Quantitatively characterize release and bioavailability of xylitol from best-behaving THXX matrices in vitro. Work shall be based on our belief that a THXX of proper solid/fluid/solid transformation properties will, under pressure and shear forces generated by occlusion of articulated posterior teeth, be delivered to and retained in the relatively sheltered confines of bicuspid and molar tooth fissures and prove efficacious for xylitol delivery to the fissure-confined plaque biofilm rich in MS for prolonged periods during the course of a day. To quantify xylitol, we shall use HPLC. However, to establish xylitol's bioavailability, without disrupting the fissure, we shall use a novel capillary analog to test whether THXXs have demonstrable anti-MS efficacy in capillary-confined space; 3. Quantitatively and qualitatively assess youngster acceptance of the THXX delivery system, using established measures of organoleptic acceptability that are likely to maximize cooperation with professional recommendations for use of THXX. Focus groups with 7-11 and 12-14 year-olds and their parents will include assessments of acceptability of different flavors and formulations. Participants will use THXX at home, then return for follow-up focus groups to provide feedback on the acceptability of taste and formulation of THXX. This will provide important information on how preteens, teens, and their parents perceive the acceptability of THXX.
Public Health Relevance Statement: Public Health Relevance: This Phase I SBIR application to develop a thixotropic xylitol-gel delivery system is responsive to 2013 NIDCR announcement of small business research topics on Infectious Diseases and Immunity. In particular, it addresses "agents to eradicate oral biofilms on teeth ...without adversely affecting the normal oral flora" and to "develop ways to interfere with microbial colonization and growth through the use of antimicrobial agents and chemotherapy."
Project Terms: 14 year old; 15 year old; 9 year old; Address; Adolescent; Affect; Age; Air; analog; Animals; Anti-Bacterial Agents; antimicrobial drug; Bacteria; base; Belief; Bicuspid; Bioavailable; Biological; Biological Availability; Blood capillaries; Businesses; capillary; Caries prevention; chemotherapy; Child; Communicable Diseases; Confined Spaces; Consumption; Dental caries; design; Drug Formulations; Dyes; Energy Metabolism; experience; Feedback; Flavoring; Focus Groups; follow-up; Food; Gel; Growth; Healthy People 2020; High Pressure Liquid Chromatography; Home environment; Human; Immunity; In Vitro; Lesion; Liquid substance; Location; Mastication; Measures; Mechanical Stress; Mechanics; Microbial Biofilms; microbial colonization; Molar tooth; Mutation; National Institute of Dental and Craniofacial Research; novel; oral bacteria; oral biofilm; Oral cavity; Parents; Participant; Phase; preadolescence; pressure; Preventive; Property; prototype; public health relevance; Recommendation; Recovery; Research; Salivary; Shelter facility; Small Business Innovation Research Grant; Solid; Streptococcus mutans; Sucrose; System; Taste Perception; Teenagers; Temperature; Testing; Time; Tooth structure; water vapor; Work; Xylitol
