Wilmore Labs, LLC, San Antonio, Texas, United States of America.
University of Texas Health Science Center at San Antonio, Psychiatry, San Antonio, Texas, United States of America.
PLoS One. 2014 Feb 26;9(2):e90131. doi: 10.1371/journal.pone.0090131. eCollection 2014.
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.
白藜芦醇提供多种生理益处，可促进各种模式生物的健康寿命，并得到临床试验的支持，继续探索白藜芦醇在人类中的治疗作用。然而，人们仍然担心白藜芦醇在人体中的生物利用度低，以及吸收和代谢的个体间差异很大，这表明非常需要开发新的白藜芦醇递送方法。我们假设，使用由白藜芦醇-赋形剂基质组成的含片进行经口腔黏膜递送，将使白藜芦醇能够快速被吸收到血液中。我们通过两项实验来验证这一概念。在第一项实验中，使用 HPLC 测定反式白藜芦醇（tRES）在水中和 2.0 M 葡萄糖、果糖、核糖、蔗糖和木糖醇溶液中的溶解度。使用带有 Bonferroni 校正的独立 t 检验比较 tRES 在每种溶液中的溶解度与水中的溶解度。tRES 在核糖溶液中的溶解度明显更高（p = 0.0013），而在其他四种溶液中的溶解度较低。鉴于 tRES 在核糖溶液中的溶解度增加，开发了一种白藜芦醇-核糖基质制成的含片，适合人类食用。制备了含片，每个含片含有 2000 毫克含片质量的 146±5.5 毫克 tRES。两名健康的人类参与者在禁食一夜后，每人服用一片准备好的含片。在给药后 15、30、45 和 60 分钟，在给药前和给药后立即进行静脉穿刺。两名参与者的 tRES 单独（即不包括白藜芦醇代谢物）的最大血浆浓度（Cmax）在给药后 15 分钟时分别为 325 和 332ng·mL（-1）。这些结果表明，与以前报道的胃肠道吸收剂型相比，白藜芦醇-核糖基质含片可以达到更高的 Cmax 并更快地进入血液。虽然这项研究受到样本量小和仅一种白藜芦醇递送方法的限制，但它确实提供了概念验证，支持进一步探索白藜芦醇给药的新递送方法。
