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Formulation and In-Vitro and In-Vivo Evaluation of a Mucoadhesive Gel Containing Freeze Dried Black Raspberries: Implications for Oral Cancer Chemoprevention

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Purpose

The purpose of these studies was to formulate mucoadhesive gels containing freeze dried black raspberries (FBR) and to determine optimum parameters for a subset of FBR bioactive compounds including anthocyanin stability, absorption and penetration in-vitro and in-vivo.

Materials and Methods

Berry gels were prepared having FBR at 5% and 10% w/w and final pHs ranging from 3.5 to 7.5. A HPLC assay was developed to quantify and determine the stability of the anthocyanins in the gels. A single time-point study was performed to determine anthocyanin uptake when the gels were applied to oral mucosa. Penetration of anthocyanins into human oral tissue explants was determined as a function of gel pH and FBR content. A HPLC-mass spectroscopy assay was utilized to quantify the anthocyanin levels in human oral tissue explants, saliva, and blood.

Results

The stability of anthocyanins in the gel was directly related to gel pH and storage temperature. Maximum stability of anthocyanins was found at lower pH (pH 3.5) and storage temperature (4°C). Anthocyanins contained in mucoadhesive berry gel formulations were readily absorbed into human oral mucosa tissue as evidenced by detectable blood levels within 5 min after gel application. There was a trend for greater penetration of anthocyanins into tissue explants for berry gels with a final pH of 6.5 versus pH 3.5.

Conclusions

Formulation and characterization of a novel gel formulation for local delivery of chemopreventive compounds to human oral mucosal tissues has been described. The results show anthocyanin stability was dependent upon gel pH and storage temperature and also demonstrate that the gel composition is well-suited for absorption and penetration into the target oral mucosal tissue site.

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Acknowledgements

The authors would like to acknowledge funding from the NIH-NCI R21CA11120 to SRM, GDS, PEL, and RJM, as well as funding from the USDA GRT961914 to GDS, SRM, and PEL.

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Authors and Affiliations

  1. Department of Oral Maxillofacial Surgery & Pathology, College of Dentistry, The Ohio State University, 305 West 12th Avenue, Columbus, Ohio, 43210-1241, USA

    Susan R. Mallery, Peter E. Larsen & Kapila A. Rodrigo

  2. Department of Orthodontics, College of Dentistry, The Ohio State University, Columbus, Ohio, USA

    Henry W. Fields

  3. The Ohio State University Comprehensive Cancer Center and Solove Research Institute, Columbus, Ohio, USA

    Gary D. Stoner

  4. Department of Food Science, College of Agriculture, The Ohio State University, Columbus, Ohio, USA

    Steven J. Schwartz & Qingguo Tian

  5. Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio, USA

    Gary D. Stoner

  6. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA

    Jin Dai & Russell J. Mumper

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  1. Susan R. Mallery
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  2. Gary D. Stoner
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Correspondence to Susan R. Mallery.

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Mallery, S.R., Stoner, G.D., Larsen, P.E. et al. Formulation and In-Vitro and In-Vivo Evaluation of a Mucoadhesive Gel Containing Freeze Dried Black Raspberries: Implications for Oral Cancer Chemoprevention. Pharm Res 24, 728–737 (2007). https://doi.org/10.1007/s11095-006-9192-1

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  • DOI: https://doi.org/10.1007/s11095-006-9192-1

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