AUTHOR=Feng Liang , Li Zhi-yong , Wang Long , Li Xing-hua , Chen Ya-ping , Yang Bing , Yang Dang , Lian Yuan-pei , Hou Xue-feng , Li Jun-hui , Ding Shu-min , Jia Xiao-bin 

TITLE=Wedelolactone-Loaded Micelles Ameliorate Doxorubicin-Induced Oxidative Injury in Podocytes by Improving Permeability and Bioavailability

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=Volume 7 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2019.00333

DOI=10.3389/fbioe.2019.00333

ISSN=2296-4185

ABSTRACT=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.