Formulation and in-vitro and in-vivo evaluation of a mucoadhesive gel containing freeze dried black raspberries: implications for oral cancer chemoprevention.
OBJECTIVE
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.


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 degrees 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.
Mallery
Susan R
SR
Department of Oral Maxillofacial Surgery & Pathology, College of Dentistry, The Ohio State University, Columbus, OH 43210-1241, USA. mallery.1@osu.edu
Stoner
Gary D
GD
Larsen
Peter E
PE
Fields
Henry W
HW
Rodrigo
Kapila A
KA
Schwartz
Steven J
SJ
Tian
Qingguo
Q
Dai
Jin
J
Mumper
Russell J
RJ
D000268:Adhesiveness; D000872:Anthocyanins / Q000032:analysis / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004355:Drug Stability; D005612:Freeze Drying; D005638:Fruit; D005782:Gels; D006801:Humans; D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry; D009061:Mouth Mucosa / Q000378:metabolism; D009062:Mouth Neoplasms / Q000517:prevention & control*; D009077:Mucins / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry; D015203:Reproducibility of Results; D027824:Rosaceae; D012463:Saliva / Q000378:metabolism; D013678:Technology, Pharmaceutical; D013696:Temperature; D046509:Tissue Culture Techniques
D000872:Anthocyanins; D016588:Anticarcinogenic Agents; D005782:Gels; D009077:Mucins; D010936:Plant Extracts