Delivery of Polyphenols in Gum for Treatment of Gingivitis

Four Tigers, Llc, Paris KY

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Periodontitis represents a polymicrobial disease, in which a complex microbial ecology that matures in biofilms in the subgingival sulcus triggers a chronic immunoinflammatory lesion that destroys soft and hard tissues of the periodontium. The ability to identify therapeutics, to enable more effective control and/or prevention of gingival inflammation, is a critical facet of current commercial strategies to improve oral health of the population. The goal of this Phase I proposal is to further develop a novel chewing gum containing blackberry extract that delivers bioactive phytochemicals to the oral cavity and test its efficacy in preventing gingivitis. The bioactive phytochemicals in the extract are polyphenols with the most notable being anthocyanins. Methods to prepare and stabilize the extract have already been developed, as well as a prototype two gram blackberry extract chewing gum. In addition, the extract has already been found to have anti-oxidant, anti-cancer, anti- inflammatory, anti-bacterial, and anti-viral properties. In this 12 month research plan, four Specific Aims are proposed as follows: Aim 1: Refine the development of chewing gum as a delivery strategy for blackberry extract as a potent, natural anti-gingivitis agent. To achieve this Aim, the Investigators will, i) complete development of qualified stability-indicating analytical method for anthocyanins and phenols in the blackberry extract and the gum prototype, ii) develop methods to extract anthocyanins and phenols from the gum, iii) determine the release rate of anthocyanins and phenols using a mechanical chewing device, iv) perform an accelerated 1 month stability study and establish preliminary release specifications for the clinical batches. Aim 2: Test the hypothesis that bioactive phytochemicals in blackberry extract inhibit mechanisms associated with gingivitis. To achieve this Aim, the Investigators will, i) evaluate the anti-inflammatory properties of the blackberry extract in human oral epithelial cells and macrophages, and ii) test the antimicrobial properties of the blackberry extract against periodontal pathogens and human herpes viruses. Four Tigers LLC, and its wholly-owned subsidiary Berryceuticals LLC, has partnered with WindStone Farms, the largest blackberry farm in the eastern part of the United States, to develop and commercialize health and medical products derived from blackberries. The investigators have assembled a highly interdisciplinary team of investigators encompassing expertise in pharmaceutics, novel drug delivery systems for the oral cavity, periodontics, immunology, and oral medicine. The chewing gum is an existing drug delivery approach that represents a practical and potentially highly versatile strategy to improve patient oral care. Specifically, the gum formulation allows for the localized release of stabilized and highly potent anti-oxidant and anti- inflammatory phytochemicals within the oral cavity. The expected outcome may be improved treatments of gingivitis and periodontal disease as well as caries, oral mucositis, and other disorders and diseases of the oral cavity. PUBLIC HEALTH RELEVANCE: The ability to identify therapeutics, to enable more effective control and/or prevention of gingival inflammation, is a critical facet of current commercial strategies to improve oral health of the population. The goal of this Phase I proposal is to further develop a novel chewing gum delivery system containing blackberry extract that delivers bioactive natural compounds to the oral cavity and test its efficacy in preventing gingivitis. The bioactive compounds in the blackberry extract are polyphenols with the most notable being anthocyanins. These polyphenols have been shown to have very significant anti-inflammatory and anti-microbial properties, among other biological activities. The expected outcome may be improved treatments of gingivitis and periodontal disease as well as caries, oral mucositis, and other disorders and diseases of the oral cavity. This product is being developed as one of the first "Botanical Drug Products" as defined by the FDA in their 2004 Guidance Document.