Pharmacokinetics of curcumin-loaded PLGA and PLGA-PEG blend nanoparticles after oral administration in rats
Pharmacokinetics of curcumin-loaded PLGA and PLGA-PEG blend nanoparticles after oral administration in rats
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DOI：
10.1016/j.colsurfb.2012.06.024
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发表时间：
2013-01-01
影响因子：
5.8
通讯作者：
Mainardes, Rubiana Mara
中科院分区：
文献类型：
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作者：
Khalil, Najeh Maissar;Frabel do Nascimento, Thuane Castro;Mainardes, Rubiana Mara
本研究的目的是评估纳米颗粒改善姜黄素药代动力学的潜力，主要目标是提高其生物利用度。通过单乳液溶剂蒸发技术获得了含有姜黄素的聚乳酸-乙醇酸（PLGA）和PLGA-聚乙二醇（PEG）（PLGA-PEG）共混纳米颗粒，粒径小于200 nm。两种配方的包封率均超过 70%。体外释放研究表明，姜黄素从 PLGA 纳米颗粒中的释放速度比从 PLGA-PEG 纳米颗粒中的释放速度慢。开发并验证了 LC-MS/MS 方法来定量大鼠血浆中的姜黄素。将纳米颗粒以单剂量口服给予大鼠，评估其药代动力学参数并与姜黄素水混悬剂进行比较。据观察，两种纳米颗粒制剂都能够随着时间的推移维持姜黄素递送，但 PLGA-PEG 纳米颗粒获得了更高的效率，在所有分析的药代动力学参数中显示出更好的结果。 PLGA 和 PLGA-PEG 纳米颗粒分别使姜黄素平均半衰期延长约 4 小时和 6 小时，姜黄素的 C-max 分别增加 2.9 倍和 7.4 倍。当姜黄素被纳米粒子，特别是PLGA-PEG纳米粒子携带时，其分布和代谢下降。负载姜黄素的 PLGA-PEG 纳米颗粒的生物利用度是 PLGA 纳米颗粒姜黄素的 3.5 倍。与姜黄素水悬浮液相比，PLGA 和 PLGA-PEG 纳米颗粒将姜黄素生物利用度分别提高了 15.6 倍和 55.4 倍。这些结果表明 PLGA，特别是 PLGA-PEG 共混纳米颗粒是姜黄素口服递送的潜在载体。 (c) 2012 Elsevier B.V. 保留所有权利。
The aim of this study was to assess the potential of nanoparticles to improve the pharmacokinetics of curcumin, with a primary goal of enhancing its bioavailability. Polylactic-co-glycolic acid (PLGA) and PLGA-polyethylene glycol (PEG) (PLGA-PEG) blend nanoparticles containing curcumin were obtained by a single-emulsion solvent-evaporation technique, resulting in particles size smaller than 200 nm. The encapsulation efficiency was over 70% for both formulations. The in vitro release study showed that curcumin was released more slowly from the PLGA nanoparticles than from the PLGA-PEG nanoparticles. A LC-MS/MS method was developed and validated to quantify curcumin in rat plasma. The nanoparticles were orally administered at a single dose in rats, and the pharmacokinetic parameters were evaluated and compared with the curcumin aqueous suspension. It was observed that both nanoparticles formulations were able to sustain the curcumin delivery over time, but greater efficiency was obtained with the PLGA-PEG nanoparticles, which showed better results in all of the pharmacokinetic parameters analyzed. The PLGA and PLGA-PEG nanoparticles increased the curcumin mean half-life in approximately 4 and 6 h, respectively, and the C-max of curcumin increased 2.9- and 7.4-fold, respectively. The distribution and metabolism of curcumin decreased when it was carried by nanoparticles, particularly PLGA-PEG nanoparticles. The bioavailability of curcumin-loaded PLGA-PEG nanoparticles was 3.5-fold greater than the curcumin from PLGA nanoparticles. Compared to the curcumin aqueous suspension, the PLGA and PLGA-PEG nanoparticles increased the curcumin bioavailability by 15.6- and 55.4-fold, respectively. These results suggest that PLGA and, in particular, PLGA-PEG blend nanoparticles are potential carriers for the oral delivery of curcumin. (c) 2012 Elsevier B.V. All rights reserved.