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用于药物释放动力学和脂质过氧化研究的多西他赛乳液的制备

The Fabrication of Docetaxel-Containing Emulsion for Drug Release Kinetics and Lipid Peroxidation.

作者信息

Wu Yifang, Wang Mengmeng, Li Yufan, Xia Hongmei, Cheng Yongfeng, Liu Chang, Xia Ying, Wang Yu, Yue Yan, Cheng Xiaoman, Xie Zili

机构信息

College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.

Clinical College of Anhui Medical University, Hefei 230601, China.

出版信息

Pharmaceutics. 2022 Sep 21;14(10):1993. doi: 10.3390/pharmaceutics14101993.

DOI:10.3390/pharmaceutics14101993
PMID:36297429
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9607308/
Abstract

Docetaxel (DTX)-based formulation development is still confronted with significant challenges, due to its refractory solubility and side effects on normal tissues. Inspired by the application of the transdermal drug delivery model to topical treatment, we developed a biocompatible and slow-release DTX-containing emulsion via self-assembly prepared by a high-speed electric stirring method and optimized the formulation. The results of accelerated the emulsion stability experiment showed that the emulsion prepared at 10,000 rpm/min had a stability of 89.15 ± 2.05%. The ADME, skin irritation, skin toxicity and molecular interaction between DTX and excipients were predicted via Discovery Studio 2016 software. In addition, DTX addition in oil or water phases of the emulsion showed different release rates in vitro and ex vivo. The DTX release ex vivo of the DTX/O-containing emulsion and the DTX/W-containing emulsion were 45.07 ± 5.41% and 96.48 ± 4.54%, respectively. In vitro antioxidant assays and anti-lipid peroxidation models revealed the antioxidant potential of DTX. However, DTX-containing emulsions could maintain and even enhance the antioxidant effect, both scavenging free radicals in vitro and inhibiting the process of lipid peroxidation.

摘要

基于多西他赛（DTX）的制剂开发仍面临重大挑战，这是由于其溶解性差以及对正常组织的副作用。受透皮给药模型在局部治疗中的应用启发，我们通过高速电搅拌法自组装制备了一种生物相容性且缓释的含DTX乳液，并对制剂进行了优化。加速乳液稳定性实验结果表明，以10,000转/分钟制备的乳液稳定性为89.15±2.05%。通过Discovery Studio 2016软件预测了DTX的体内药物代谢动力学、皮肤刺激性、皮肤毒性以及DTX与辅料之间的分子相互作用。此外，在乳液的油相或水相中添加DTX在体外和离体实验中显示出不同的释放速率。含DTX/O乳液和含DTX/W乳液的DTX离体释放率分别为45.07±5.41%和96.48±4.54%。体外抗氧化试验和抗脂质过氧化模型揭示了DTX的抗氧化潜力。然而，含DTX乳液既能维持甚至增强抗氧化作用，在体外清除自由基，又能抑制脂质过氧化过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/9607308/4fdf7110668c/pharmaceutics-14-01993-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/9607308/36c07e553970/pharmaceutics-14-01993-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/9607308/220981b5ccb0/pharmaceutics-14-01993-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/9607308/cda9dcea7229/pharmaceutics-14-01993-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/9607308/c000803d5f6b/pharmaceutics-14-01993-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/9607308/b5c85945a5e2/pharmaceutics-14-01993-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/9607308/dbe5cef7c0ed/pharmaceutics-14-01993-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/9607308/479a47f57d8b/pharmaceutics-14-01993-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/9607308/4fdf7110668c/pharmaceutics-14-01993-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/9607308/36c07e553970/pharmaceutics-14-01993-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/9607308/220981b5ccb0/pharmaceutics-14-01993-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/9607308/cda9dcea7229/pharmaceutics-14-01993-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/9607308/c000803d5f6b/pharmaceutics-14-01993-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/9607308/b5c85945a5e2/pharmaceutics-14-01993-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/9607308/dbe5cef7c0ed/pharmaceutics-14-01993-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/9607308/479a47f57d8b/pharmaceutics-14-01993-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/9607308/4fdf7110668c/pharmaceutics-14-01993-g008.jpg

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