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1.  Development of a Lozenge for Oral Transmucosal Delivery of Trans-Resveratrol in Humans: Proof of Concept 
PLoS ONE  2014;9(2):e90131.
Resveratrol provides multiple physiologic benefits which promote healthspan in various model species and clinical trials support continued exploration of resveratrol treatment in humans. However, there remains concern regarding low bioavailability and wide inter-individual differences in absorption and metabolism in humans, which suggests a great need to develop novel methods for resveratrol delivery. We hypothesized that oral transmucosal delivery, using a lozenge composed of a resveratrol-excipient matrix, would allow resveratrol to be absorbed rapidly into the bloodstream. We pursued proof of concept through two experiments. In the first experiment, the solubility of trans-resveratrol (tRES) in water and 2.0 M solutions of dextrose, fructose, ribose, sucrose, and xylitol was determined using HPLC. Independent t-tests with a Bonferroni correction were used to compare the solubility of tRES in each of the solutions to that in water. tRES was significantly more soluble in the ribose solution (p = 0.0013) than in the other four solutions. Given the enhanced solubility of tRES in a ribose solution, a resveratrol-ribose matrix was developed into a lozenge suitable for human consumption. Lozenges were prepared, each containing 146±5.5 mg tRES per 2000 mg of lozenge mass. Two healthy human participants consumed one of the prepared lozenges following an overnight fast. Venipuncture was performed immediately before and 15, 30, 45, and 60 minutes following lozenge administration. Maximal plasma concentrations (Cmax) for tRES alone (i.e., resveratrol metabolites not included) were 325 and 332 ng⋅mL−1 for the two participants at 15 minute post-administration for both individuals. These results suggest a resveratrol-ribose matrix lozenge can achieve greater Cmax and enter the bloodstream faster than previously reported dosage forms for gastrointestinal absorption. While this study is limited by small sample size and only one method of resveratrol delivery, it does provide proof of concept to support further exploration of novel delivery methods for resveratrol administration.
doi:10.1371/journal.pone.0090131
PMCID: PMC3935991  PMID: 24587240
2.  The planar cell polarity effector Fuz is essential for targeted membrane trafficking, ciliogenesis, and mouse embryonic development 
Nature cell biology  2009;11(10):1225-1232.
The planar cell polarity (PCP) signaling pathway is essential for embryonic development because it governs diverse cellular behaviors, and the “core PCP” proteins, such as Dishevelled and Frizzled, have been extensively characterized1–4. By contrast, the “PCP effector” proteins, such as Intu and Fuz, remain largely unstudied5, 6. These proteins are essential for PCP signaling, but they have never been investigated in a mammal and their cell biological activities remain entirely unknown. We report here that Fuz mutant mice display neural tube defects, skeletal dysmorphologies, and Hedgehog signaling defects stemming from disrupted ciliogenesis. Using bioinformatics and imaging of an in vivo mucociliary epithelium, we establish a central role for Fuz in membrane trafficking, showing that Fuz is essential for trafficking of cargo to basal bodies and to the apical tips of cilia. Fuz is also essential for exocytosis in secretory cells. Finally, we identify a novel, Rab-related small GTPase as a Fuz interaction partner that is also essential for ciliogenesis and secretion. These results are significant because they provide novel insights into the mechanisms by which developmental regulatory systems like PCP signaling interface with fundamental cellular systems such as the vesicle trafficking machinery.
doi:10.1038/ncb1966
PMCID: PMC2755648  PMID: 19767740

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