Laboratory of Mitochondrial and Metabolism, Department of Anesthesiology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China.
Laboratory of Anesthesia and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China.
Drug Deliv. 2021 Dec;28(1):433-444. doi: 10.1080/10717544.2021.1886198.
Nicotinamide riboside (NR), as a dietary supplement, can be converted to nicotinamide adenine dinucleotide (NAD) in cells to support mitochondrial energy metabolism. However, the efficacy of oral administrated NR is limited due to its quick degradation in circulation and low bioavailability in targeted organs. In this study, we fabricated nanocrystal self-assembled microspheres by Nano Spray Dryer for oral delivery of NR. The structure of NR and resveratrol (RES) nanocrystal self-assembled microspheres (NR/RESms) is confirmed by the morphology, chemical structure, and crystallization. The NR/RESms displayed restricted NR release at the gastric acid-mimic condition (<15% in the first 8 hours), while achieved accelerated NR release in an enteric-mimic environment (>46% within 8 hours). Oral administration of NR/RESms for 8 hours significantly elevated NAD levels in serum (169.88 nM versus 30.93 nM in the NR group, < .01; and 66.89 nM in the NR + RES group, < .05), and enhanced NAD abundance in multiple organs in mice, exhibiting an improved oral NAD bioavailability. In addition, without any serious adverse effects on major organs, oral delivery of NR/RESms attenuated myocardial infarction (15.82% versus 19.38% in the I/R + NR group and 20.76% in the I/R + NR + RES group) in a cardiac ischemia/reperfusion (I/R) injury mouse model. Therefore, our data supported that the NR/RESms is a promising candidate as NAD booster for oral administration.
烟酰胺核糖（NR）作为膳食补充剂，可以在细胞内转化为烟酰胺腺嘌呤二核苷酸（NAD），以支持线粒体能量代谢。然而，由于其在循环中迅速降解和在靶向器官中的生物利用度低，口服给予 NR 的效果有限。在这项研究中，我们通过纳米喷雾干燥器制造了纳米晶体自组装微球，用于 NR 的口服给药。NR 和白藜芦醇（RES）纳米晶体自组装微球（NR/RESms）的结构通过形态、化学结构和结晶得到证实。NR/RESms 在模拟胃酸的条件下（8 小时内<15%）显示出受限的 NR 释放，而在模拟肠液的环境中则实现了加速的 NR 释放（8 小时内>46%）。口服给予 NR/RESms 8 小时可显著提高血清中的 NAD 水平（NR 组为 30.93 nM，NR 组为 169.88 nM，<0.01；NR+RES 组为 66.89 nM，<0.05），并增强了小鼠多个器官中的 NAD 丰度，口服 NAD 生物利用度得到改善。此外，口服给予 NR/RESms 不会对主要器官造成任何严重的不良影响，可减轻心肌缺血/再灌注（I/R）损伤小鼠模型中的心肌梗死（I/R+NR 组为 19.38%，I/R+NR+RES 组为 15.82%）。因此，我们的数据支持 NR/RESms 是一种有前途的口服 NAD 增强剂候选物。
