SBIR-STTR Award

Topical fluorides have been the mainstay in the prevention of dental caries for decades. However, topical fluoride alone is not enough to thwart tooth decay in high-risk populations. The purpose of this Phase I application is to determine the technical and scientific feasibility of using a combination povidone-iodine (PVP-I)-5% sodium fluoride (NaF) varnish as a potential commercial product to prevent dental caries. The research will be conducted by the small business firm ADP Silver Dental Arrest, LLC, in collaboration with experienced researchers at the University of Washington Northwest Center to Reduce Oral Health Disparities. The Premier Dental Products Company will prepare the varnish to the specifications of the applicant at no cost to the grant. The Specific Aims of this Phase I SBIR are to: (1) Demonstrate that a new povidone iodine-sodium fluoride varnish has antimicrobial activity and fluoride bioavailability and enamel remineralization ability. (a) Use the in vitro moel developed by Castillo and colleagues to determine the bioavailability of fluoride and iodine release from an experimental povidone-iodine- sodium fluoride varnish; (b) Use an in vitro model of Tanzer and colleagues to assess the additive (indifferent), potentially synergistic, or potentially antagonistic effects of sodium fluoride and povidone-iodine against Streptococcus mutans using the criteria of Eliopoulos and Moellering; (c) Use a slight modification the Featherstone laboratory pH cycling model to test remineralization. (2) Assess the esthetic and organoleptic properties of the new povidone iodine-sodium fluoride varnish. Caries researchers for sometime have suggested strategies that combine an antiseptic with topical fluoride to reduce or eliminate the oral cariogenic bacteria reservoir in addition to topical fluoride which primarily remineralizes teeth enamel. Povidone-iodine is an FDA-approved and widely used bactericidal antiseptic. For the oral flora, iodine has preferential activities against streptococcl species. Moreover, iodine's effectiveness may last as long as six months.

Public Health Relevance Statement:


Public Health Relevance:
In this application we propose to: (1) use an in vitro model to determine the bioavailability of fluoride and iodine release from a povidone-iodine-sodium fluoride varnish; (2) use an in vitro model to assess the additive, potentially synergistic, or antagonistic effects of sodium fluoride and povidone-iodine against Streptococcus mutans, the primary pathogens in human dental caries; 3) use a pH cycling model to test remineralization; and 4) assess the organoleptic characteristics of test varnishes.

NIH Spending Category:
Dental/Oral and Craniofacial Disease; Infectious Diseases; Pediatric; Pediatric Research Initiative; Prevention

Project Terms:
Acids; Adolescent; Adult; Age; Anti-Bacterial Agents; antimicrobial; Bacteria; Bacterial Infections; bactericide; base; Biological; Biological Availability; Businesses; Carbohydrates; Caries prevention; cariogenic bacteria; Characteristics; Child; Childhood; Chronic; Chronic Disease; Collaborations; cost; Data; Dental; Dental caries; Dental Enamel; Dental Plaque; Diet; Disease; Effectiveness; Esthetics; ethnic disadvantage; ethnic minority population; experience; FDA approved; Fluoride Varnishes; Fluorides; Fostering; Glycolysis Inhibition; Grant; health disparity; high risk; Human; In Vitro; in vitro Model; in vivo; Iodine; Kinetics; Laboratories; Local Anti-Infective Agents; Marketing; Modeling; Modification; Oral; oral bacteria; Oral health; Pain; pathogen; Pharmacologic Substance; Phase; Population; Povidone-Iodine; Prevalence; prevent; Property; public health relevance; remineralization; Reporting; Research; Research Personnel; Silver; Small Business Innovation Research Grant; Sodium Fluoride; Streptococcus mutans; Surgeon; Systemic infection; Testing; Tooth structure; Topical Fluorides; Universities; Varnish; Virulence Factors; Washington; Xerostomia

This Small Business Innovation Research Phase II proposal to NIH requests $1,424,585 support for Advantage Silver Dental Arrest, LLC to conduct a Phase II RCT to determine the efficacy of Advantage Anti- Caries Varnish, a combination povidone-iodine-sodium fluoride varnish, with the primary outcome of dental caries increment at 2 years post baseline. This proposal responds to NIDCR research topics: F. Develop ways to interfere with microbial colonization and growth through the use of antimicrobial agents and chemotherapy (Infectious Diseases and Immunity) and **D. Develop and test for safety, efficacy, and/or effectiveness of measures or materials for diagnosing, preventing, or treating oral, dental, and craniofacial conditions and disorders (Clinical and Behavioral Research). The significance is that the agent developed by Advantage Silver Dental Arrest, LLC in Phase I builds on the current mainstay of caries prevention, NaF varnish but adds a safe antibacterial agent that may prove synergistic with F; and as a decay-preventive modality, varnish is inexpensive, easy to use, and well tolerated by patients of all ages and special needs. This effort also brings research partners that have a strong track record in microbiology, caries research, and public health together with experienced oral care industry/business partners who have a long history of successfully bringing products to market. This research addresses Healthy People 2020 objective OH-1 Reduce the proportion of children and adolescents who have dental caries experience in their primary or permanent teeth. It also addresses Goals 1, 3 and 4 of the NIDCR Strategic Plan 2009-2013. The proposed work is innovative because the resulting product takes advantage of possible biological synergies and could change the standard of care. Moreover, because the FDA has granted an IND and a Phase I safety study has been conducted, the product is ready for Phase II RCT. An easy to use single product will speed dissemination and reduce barriers to adoption. The size of the United States topical fluoride market is estimated to total $185 - $205 million annually. We conservatively expect to capture between 5% and 10% of the U.S market 3 years post FDA NDA approval. Germany and Australia represent significant additional revenue opportunities due to their size, their focus on preventive oral care, reasonable costs of market entry and manageable regulatory hurdles. Additional market opportunities outside the U.S will also be explored and pursued where appropriate. Key words: dental caries; sodium fluoride; povidone iodine; varnish

Public Health Relevance Statement:
PROJECT NARRATIVE Dental caries (tooth decay) is a common disease. Advantage Silver Dental Arrest, LLC. proposes to conduct a Phase II RCT to determine the efficacy of Advantage Anti-Caries Varnish, a combination povidone-iodine- sodium fluoride varnish. The new agent developed in Phase I builds on the current mainstay of caries prevention, NaF varnish but adds a safe antibacterial agent that may prove synergistic with F. As a decay- preventive modality, varnish is inexpensive, easy to use, and well tolerated by patients of all ages and special needs. This research addresses Healthy People 2020 objective OH-1 Reduce the proportion of children and adolescents who have dental caries experience in their primary or permanent teeth.

NIH Spending Category:
Dental/Oral and Craniofacial Disease; Infectious Diseases; Patient Safety; Pediatric; Pediatric Research Initiative; Prevention

Project Terms:
Acids; Address; Adolescent; Adoption; Adult; Age; Anti-Bacterial Agents; antimicrobial drug; Australia; Award; Bacteria; Bacterial Infections; bactericide; Behavioral Research; Biological; Businesses; Carbohydrates; Caries prevention; cariogenic bacteria; Child; Childhood; Chronic; Chronic Disease; Clinical; Clinical Protocols; Clinical Research; Cohort Studies; Collaborations; Communities; Consent Forms; cost; craniofacial; deciduous tooth; demineralization; Dental; Dental caries; Dental Plaque; Dental Research; Diagnosis; Diet; Disease; Effectiveness; effectiveness measure; Enrollment; Ensure; ethnic disadvantage; ethnic minority population; Evaluation; experience; FDA approved; Federated States of Micronesia; Fluoride Varnishes; Fluorides; Germany; Glycolysis Inhibition; Goals; Grant; Growth; Healthy People 2020; high risk; Immunity; In Vitro; in vivo; Industry; infectious disease chemotherapy; innovation; Institutional Review Boards; Intervention; Intervention Studies; Iodine; Lesion; Local Anti-Infective Agents; Manuals; Marketing; Meta-Analysis; microbial colonization; Microbiology; Modality; Monitor; National Institute of Dental and Craniofacial Research; New Agents; Oral; oral bacteria; oral care; Pain; Patients; permanent tooth; Pharmacologic Substance; Phase; Population; Povidone-Iodine; Prevalence; prevent; Preventive; primary outcome; Procedures; Protocols documentation; public health research; Recording of previous events; Reporting; Research; Research Design; Research Personnel; Safety; safety study; safety testing; Schedule; Silver; Site; Small Business Innovation Research Grant; Sodium Fluoride; Speed; standard of care; Strategic Planning; Streptococcus; Streptococcus mutans; Surgeon; systematic review; Systemic infection; Testing; Time; Tooth Remineralization; Tooth structure; Topical Fluorides; United States; United States National Institutes of Health; Universities; Varnish; Virulence; Washington; Work; Writing; Xerostomia