Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, Zhejiang 314001, PR China.
Mol Pharm. 2022 Sep 5;19(9):3057-3074. doi: 10.1021/acs.molpharmaceut.2c00455. Epub 2022 Aug 16.
Curcumin nanoformulations for intravenous injection have been developed to offset poor absorption, biotransformation, degradation, and excessive clearance associated with parenteral delivery. This review investigates (1) whether intravenous nanoformulations improve curcumin pharmacokinetics (PK) and (2) whether improved PK yields greater therapeutic efficacy. Standard PK parameters (measured maximum concentration [], area under the curve [AUC], distribution volume [], and clearance [CL]) of intravenously administered free curcumin in mice and rats were sourced from literature and compared to curcumin formulated in nanoparticles, micelles, and liposomes. The studies that also featured analysis of pharmacodynamics (PD) in murine cancer models were used to determine whether improved PK of nanoencapsulated curcumin resulted in improved PD. The distribution and clearance of free and nanoformulated curcumin were very fast, typically accounting for >80% curcumin elimination from plasma within 60 min. Case-matched analysis demonstrated that curcumin nanoencapsulation generally improved curcumin PK in terms of measured ( = 27) and AUC ( = 33), and to a lesser extent and CL. However, when the data were unpaired and clustered for comparative analysis, only 5 out of the 12 analyzed nanoformulations maintained a higher relative curcumin concentration in plasma over time compared to free curcumin. Quantitative analysis of the mean plasma concentration of free curcumin versus nanoformulated curcumin did not reveal an overall marked improvement in curcumin PK. No correlation was found between PK and PD, suggesting that augmentation of the systemic presence of curcumin does not necessarily lead to greater therapeutic efficacy.
姜黄素静脉注射纳米制剂的开发旨在克服与注射给药相关的吸收不良、生物转化、降解和过度清除。本综述调查了：（1）静脉纳米制剂是否改善姜黄素的药代动力学（PK）；（2）改善的 PK 是否产生更大的治疗效果。从文献中获取了静脉给予游离姜黄素在小鼠和大鼠中的标准 PK 参数（最大浓度 [Cmax]、曲线下面积 [AUC]、分布容积 [Vd] 和清除率 [CL]），并将其与纳米粒子、胶束和脂质体中的姜黄素进行比较。还使用了在小鼠癌症模型中进行药效学（PD）分析的研究来确定纳米封装姜黄素改善 PK 是否导致 PD 改善。游离和纳米制剂姜黄素的分布和清除速度非常快，通常在 60 分钟内超过 80%的姜黄素从血浆中消除。病例匹配分析表明，姜黄素纳米封装通常在 Cmax（ = 27）和 AUC（ = 33）方面改善姜黄素 PK，在 （ = 33）和 CL 方面改善较小。然而，当数据未配对并为比较分析聚类时，12 种分析的纳米制剂中只有 5 种在一段时间内在血浆中的游离姜黄素的相对浓度保持较高。游离姜黄素与纳米制剂姜黄素的平均血浆浓度的定量分析并未显示姜黄素 PK 的总体明显改善。PK 和 PD 之间未发现相关性，表明姜黄素在系统中存在的增加不一定导致更大的治疗效果。
