Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration.
Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration.
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DOI：
10.2147/ijn.s107442
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发表时间：
2016
影响因子：
8
通讯作者：
Miyazawa T
中科院分区：
文献类型：
--
作者：
Harigae T;Nakagawa K;Miyazawa T;Inoue N;Kimura F;Ikeda I;Miyazawa T
姜黄素（CUR）是姜黄中的主要多酚，口服后吸收不良且代谢迅速，严重降低了其生物利用度。最近有人建议基于聚乳酸-乙醇酸共聚物的 CUR 纳米颗粒 (CUR-NP) 可以提高 CUR 的生物利用度，但这尚未得到充分验证。具体来说，没有关于姜黄素葡萄糖苷酸 (CURG) 的数据，姜黄素葡萄糖醛酸是口服 CUR-NP 后在血浆中发现的 CUR 的主要代谢物。在此，我们研究了 CUR-NP 的吸收和代谢，并评估了 CUR-NP 是否提高了 CUR 的生物利用度。大鼠口服 CUR-NP 后，我们使用高效液相色谱-串联质谱分析了 CUR 及其代谢物的血浆和器官分布。为了阐明 CUR-NP 增加肠道吸收的机制，我们制备了由磷脂酰胆碱和胆汁盐组成的混合胶束，并检测了 CUR-NP 的胶束溶解度。此外，我们研究了所得胶束与分化的 Caco-2 人肠细胞的细胞掺入。体内给予 CUR-NP 后，CUR 被有效吸收，并主要以 CURG 形式存在于血浆中，与其他器官相比，血浆中含有大量的代谢物。因此，CUR-NP 增加了 CUR 的肠道吸收，而不是减少代谢降解和向其他代谢物的转化。在体外，封装在 CUR-NP 中的 CUR 溶解在混合胶束中；然而，胶束中是否含有CUR或CUR-NP对细胞摄取效率影响不大。因此，我们认为 CUR-NP 在混合胶束中的高溶解能力，而不是细胞摄取效率，解释了 CUR-NP 在体内的高肠道吸收。这些发现有助于更好地了解口服给药后 CUR 和 CUR-NP 的生物利用度。为了提高CUR的生物利用度，未来的研究应集中于增强CUR对代谢降解的抵抗力以及CUR向其他代谢物的转化，这可能会在食品功能和疾病预防方面带来新的发现。
Curcumin (CUR), the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid)-based CUR nanoparticles (CUR-NP) have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG), the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability. Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells. Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with other organs. Thus, CUR-NP increased intestinal absorption of CUR rather than decreasing metabolic degradation and conversion to other metabolites. In vitro, CUR encapsulated in CUR-NP was solubilized in mixed micelles; however, whether the micelles contained CUR or CUR-NP had little influence on cellular uptake efficiency. Therefore, we suggest that the high solubilization capacity of CUR-NP in mixed micelles, rather than cellular uptake efficiency, explains the high intestinal absorption of CUR-NP in vivo. These findings provide a better understanding of the bioavailability of CUR and CUR-NP following oral administration. To improve the bioavailability of CUR, future studies should focus on enhancing the resistance to metabolic degradation and conversion of CUR to other metabolites, which may lead to novel discoveries regarding food function and disease prevention.