Enhancement of Curcumin Bioavailability Via the Prodrug Approach: Challenges and Prospects
Enhancement of Curcumin Bioavailability Via the Prodrug Approach: Challenges and Prospects
复制标题
DOI：
10.1007/s13318-016-0377-7
复制
发表时间：
2017-06-01
影响因子：
1.9
通讯作者：
Rojsitthisak, Pornchai
中科院分区：
文献类型：
--
作者：
Bhuket, Pahweenvaj Ratnatilaka Na;El-Magboub, Asma;Rojsitthisak, Pornchai
姜黄素是一种天然产物，具有许多有趣的药理学性质。然而，这些被特别差的生物制药性质所抵消。姜黄素在人体中的口服生物利用度非常低，主要是由于溶解度低，稳定性差和广泛的代谢。这导致了多种方法来提高生物利用度，包括姜黄素与代谢抑制剂一起给药，配制成纳米颗粒，姜黄素结构的修饰和姜黄素前药的开发。在本文中，我们专注于这些方法的药代动力学结果。姜黄素从前药释放后的药代动力学参数取决于姜黄素和前体之间的连接体，并且释放本身可能取决于切割位点处的生理和酶促环境。这是一个需要更多数据来合理设计改进接头的领域。姜黄素前药的细胞毒性似乎与体外细胞摄取密切相关，但体内相关性尚不确定。我们的结论是，改进的实验和理论模型的吸收姜黄素前药，准确的分析方法，同时测量血浆水平的前药和释放姜黄素的发展，并在动物模型中获得更多的药代动力学数据的剂量预测在人类需要促进运动的姜黄素前药进入临床试验。
Curcumin is a natural product with many interesting pharmacological properties. However, these are offset by the particularly poor biopharmaceutical properties. The oral bioavailability of curcumin in humans is very low, mainly due to low solubility, poor stability, and extensive metabolism. This has led to multiple approaches to improve bioavailability, including administration of curcumin with metabolism inhibitors, formulation into nanoparticles, modification of the curcumin structure, and development of curcumin prodrugs. In this paper, we focus on the pharmacokinetic outcomes of these approaches. Pharmacokinetic parameters of curcumin after release from prodrugs are dependent on the linker between curcumin and the promoiety, and the release itself may depend on the physiological and enzymatic environment at the site of cleavage. This is an area in which more data are required for rational design of improved linkers. Cytotoxicity of curcumin prodrugs seems to correlate well with cellular uptake in vitro, but the in vivo relevance is uncertain. We conclude that improved experimental and theoretical models of absorption of curcumin prodrugs, development of accurate analytical methods for simultaneous measurement of plasma levels of prodrug and released curcumin, and acquisition of more pharmacokinetic data in animal models for dose prediction in humans are required to facilitate movement of curcumin prodrugs into clinical trials.