Distribution of anthocyanins delivered from a bioadhesive black raspberry gel following topical intraoral application in normal healthy volunteers.
OBJECTIVE
Results from our oral cavity chemoprevention trial demonstrated appreciable interpatient variations regarding chemopreventive efficacy of a freeze dried black raspberry (FBR) gel. We speculated these data reflected individual patient-related differences in absorption, target tissue uptake and local compound metabolism of key FBR compounds (anthocyanins). Accordingly, this study assessed the distribution of anthocyanins from the 10% (w/w) FBR gel in saliva, oral tissues and plasma.


METHODS
Human subject participation entailed collection of: (1) saliva, tissue and plasma (5 min following gel application, keratinized tissues), (2) saliva and plasma (5 min after sublingual gel application), (3) saliva and plasma at 1, 2, and 4 h post gel application (keratinized tissues), and (4) saliva (cyanidin 3-rutinoside incubations). Levels of FBR anthocyanins in the respective samples were analyzed by LC/MS/MS.


RESULTS
Our data show: significantly higher anthocyanin levels in saliva and oral tissues relative to matched plasma samples, marked donor-specific variations in anthocyanin uptake, sustainability of anthocyanins at the target site, pH affects anthocyanin penetration and intraoral anthocyanin decomposition and/or metabolism.


CONCLUSIONS
No previous oral cavity chemoprevention trials evaluated compound distribution at the treatment site. Our data, which demonstrate a local delivery-derived pharmacologic advantage, provide insights which could advance oral cavity chemoprevention strategies.
Ugalde
Carlos M
CM
Division of Oral Maxillofacial Surgery, Pathology & Anesthesiology, College of Dentistry, The Ohio State University, Columbus, Ohio, USA.
Liu
Zhongfa
Z
Ren
Chen
C
Chan
Kenneth K
KK
Rodrigo
Kapila A
KA
Ling
Yhonghua
Y
Larsen
Peter E
PE
Chacon
Guillermo E
GE
Stoner
Gary D
GD
Mumper
Russell J
RJ
Fields
Henry W
HW
Mallery
Susan R
SR
D000268:Adhesiveness; D000284:Administration, Oral; D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000872:Anthocyanins / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D001711:Biotransformation; D002853:Chromatography, Liquid; D005260:Female; D005782:Gels; D006801:Humans; D008297:Male; D009055:Mouth / Q000378:metabolism*; D019647:Oral Surgical Procedures; D028321:Plant Preparations / Q000493:pharmacokinetics; D027824:Rosaceae; D012463:Saliva / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution; D055815:Young Adult
D000872:Anthocyanins; D016588:Anticarcinogenic Agents; D005782:Gels; D028321:Plant Preparations