Our labs recently showed that application of a 10%-freeze dried-black-raspberry (FBR) gel to premalignant oral epithelial lesions elicited positive therapeutic effects. While gel delivery enables targeted tissue uptake, oral cancer is speculated to arise from a field-cancerization effect. Rinses that provide a more generalized distribution of chemopreventives could enhance therapeutic benefits.
Objective: This study compared the abilities of three FBR rinses to provide sustained salivary levels of anthocyanins (the predominant phenolics and key FBR chemopreventives).
Methods: Pharmacokinetic analyses of salivary levels of FBR-anthocyanins [cyanidin-3-rutinoside, cyanidin-3-xylosylrutinoside, cyanidin-3-glucoside, cyanidin-3-sambubioside)] were conducted via LC/MS/MS. Rinse compositions (10% FBR final concentration) were: Rinse1=dH2O, Rinse2=equal parts Ora-Plus™, Ora-Sweet-SF™, glycerin, + chlorhexidine gluconate (final=0.12%), Rinse3=Rinse2 without chlorhexidine gluconate. Participants (n=10) evaluated all three rinses on consecutive weeks and provided saliva samples at: baseline, 0,5,30,60,120,240 minutes following a three minute vigorous rinse (n.p.o. after rinsing). Intradonor levels of total anthocyanins (accounting for volume dilution) were analyzed by the Friedman Two-Way Analysis of Variance by Ranks, while total molarity was compared via the Kruskal Wallis ANOVA followed by a Dunns Multiple Comparison test, with á established at p<0.05.
Results: Rinse1 provided: 1) significantly higher total µg levels of cyanidin-3-glucoside (t0), cyanidin-3-rutinoside (t0, 240), cyanidin-3-sambubioside (t0, 30, 60, 240), cyanidin-3-xylosylrutinoside (t30, 60, 240); 2) significantly higher final molarity of cyanidin-3-rutinoside (t240), cyanidin-3-sambubioside (t60, 240), cyanidin-3-xylosylrutinoside (t30, 60, 240); 3) significantly lower saliva volumes at t5; 4) higher mean levels of all anthocyanins (3.2 fold+0.4 s.e.m., n=16) at all time points relative to gel data. Interdonor ranges in anthocyanin levels (mean+s.e.m.) were highest in Rinse2: Rinse3=9.4+2.0, Rinse1=33.8+13.8, Rinse2=63.0+47.1. Ongoing studies are evaluating Phase II enzyme-anthocyanin metabolism and bioactivation via aglycone formation.
Conclusions: These data imply concurrent use of gel+rinse formulations could potentiate FBRs' chemopreventive effects.
[R01CA95901, R01CA129609, R21CA132138, T32DE14320]