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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Bioeng. Biotechnol. | doi: 10.3389/fbioe.2019.00333

Wedelolactone-loaded micelles ameliorates doxorubicin-induced oxidative injury in podocytes by improving permeability and bioavailability

 Liang Feng1*, Zhi-Yong Li2,  Long Wang1, Xing-Hua Li1, Ya-Ping Chen1, Bing Yang3, Dang Yang3, Yuan-Pei Lian1,  Xuefeng Hou1, Jun-Hui Li4,  Shumin Ding5 and Xiao-Bin Jia1*
  • 1China Pharmaceutical University, China
  • 2Minzu University of China, China
  • 3Nanjing University of Chinese Medicine, China
  • 4Department of Nephrology, Shanghai Sixth People's Hospital, China
  • 5Changzhou University, China

Wedelolactone (WED) is commonly used for the treatment of doxorubicin (DOX) - induced kidney damage, but its efficacy is limited by its poor solubility and bioavailability. In this study, we developed a novel delivery system of WED-loaded micelles (WED-M) with Solutol® HS15 and lecithin at an optimized ratio of 7:3 to improve the poor permeability and bioavailability of WED and to enhance its efficacy. The spherical-shaped WED-M (particle size : 160.5±3.4 nm; zeta potential : -30.1±0.9 mV; entrapment efficiency: 94.41±1.64%; drug loading: 8.58±0.25%; solubility: 1.89±0.06 mg/ml) has a continuous stability within 14 days and a sustained release profile. The permeability of WED-M in Caco-2 cells indicated a significant 1.61-fold higher of Papp AP to BL than WED only. Additionally, pharmacokinetics evaluation of WED-M demonstrated the bioavailability of WED was increased by 2.78-fold. Both HE staining and transmission electron microscope observed an obvious improvement on pathological damage in WED-M treatment. Moreover, WED-M significantly enhanced ROS level in mice and podocytes MPC5 cells. We concluded that the micelles delivery system WED could improve its permeability and bioavailability to attenuate DOX- induced oxidative injury in podocytes. This study provided important information on a fact that micelles delivery system WED-M showed a significant improvement on renal damage.

Keywords: Wedelolactone, micelles, nephrotoxicity, Oxidative Stress, Podocytes

Received: 31 Jul 2019; Accepted: 30 Oct 2019.

Copyright: © 2019 Feng, Li, Wang, Li, Chen, Yang, Yang, Lian, Hou, Li, Ding and Jia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mx. Liang Feng, China Pharmaceutical University, Nanjing, 210009, Jiangsu Province, China, wenmoxiushi@163.com
Mx. Xiao-Bin Jia, China Pharmaceutical University, Nanjing, 210009, Jiangsu Province, China, jiaxiaobin2015@163.com