Enhancing the Delivery of Resveratrol in Humans: If Low Bioavailability is the Problem, What is the Solution?

Abstract

Abstract:Resveratrol has emerged as a leading candidate for improving healthspan through potentially slowing the aging process and preventing chronic diseases. The poor bioavailability of resveratrol in humans has been a major concern for translating basic science findings into clinical utility. Although a number of positive findings have emerged from human clinical trials, there remain many conflicting results, which may partially be attributed to the dosing protocols used. A number of theoretical solutions have been developed to improve the bioavailability of resveratrol, including consumption with various foods, micronized powders, combining it with additional phytochemicals, controlled release devices, and nanotechnological formulations. While laboratory models indicate these approaches all have potential to improve bioavailability of resveratrol and optimize its clinical utility, there is surprisingly very little data regarding the bioavailability of resveratrol in humans. If bioavailability is indeed a limitation in the clinical utility of resveratrol, there is a need to further explore methods to optimize bioavailability in humans. This review summarizes the current bioavailability data, focusing on data from humans, and provides suggested directions for future research in this realm.

Combinatorial resveratrol and quercetin polymeric micelles mitigate doxorubicin induced cardiotoxicity in vitro and in vivo

“…[25,26] Therefore, while in vitro release kinetics do not directly correlate with in vivo circulating times, it is anticipated that the half-life of RES in mRQ will be greater than free RES (1.8 hr) in humans. [27] While QUE has a long terminal half-life (11 hr), its oral bioavailability (< 1 %), and aqueous solubility (2.2 µg/mL) are low. [16,20] Intravenous micellar delivery of QUE mitigates both the solubility concerns and the oral bioavailability issues.…”

3′-hydroxy-3,4,5,4′-tetramethoxystilbene, the metabolite of resveratrol analogue DMU-212, inhibits ovarian cancer cell growth in vitro and in a mice xenograft model

“…Although the pleiotropic activities of resveratrol have been revealed, its therapeutic potential is limited due to low bioavailability and rapid elimination from the body3. Therefore, structural modifications of the resveratrol scaffold have been conducted to produce synthetic derivatives with improved pharmacokinetic parameters.…”

Preclinical formulation for the pharmacokinetics and efficacy of GBO-006, a selective polo like kinase 2 (PLK2) inhibitor for the treatment of triple negative breast cancer

“…GBO-006 showed very poor oral bioavailability (2-6 %) across mice, rats and dogs ( Figures 3, 4 and 6). Potential causes for the low oral bioavailability could be due to metabolism in the gut wall, and first-pass metabolism in the liver [17][18][19]. Following intravenous dosing to mice, rats and dogs, GBO-006 is rapidly eliminated from plasma within the first several hours with half-life estimates ranging from 0.5 to 0.7 h over this period.…”