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

Autor:	Feng L; School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China., Li ZY; China Minority Traditional Medical Center, Minzu University of China, Beijing, China., Wang L; School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China., Li XH; School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China., Chen YP; School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China., Yang B; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China., Yang D; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China., Lian YP; School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China., Hou XF; School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China., Li JH; Department of Nephrology, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai, China., Ding SM; School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou, China., Jia XB; School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China.; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Jazyk:	angličtina
Zdroj:	Frontiers in bioengineering and biotechnology [Front Bioeng Biotechnol] 2019 Nov 22; Vol. 7, pp. 333. Date of Electronic Publication: 2019 Nov 22 (Print Publication: 2019).
DOI:	10.3389/fbioe.2019.00333
Abstrakt:	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 spherically 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 continuous stability over 14 days and a sustained release profile. The permeability of WED-M in Caco-2 cells indicated a significant 1.61-fold higher Papp AP to BL ratio than WED alone. Additionally, pharmacokinetic evaluation of WED-M demonstrated that the bioavailability of WED was increased 2.78-fold. Both HE staining and transmission electron microscopy showed an obvious improvement of pathological damage in WED-M treatment. Moreover, WED-M significantly enhanced the ROS level in mice and MPC5 podocytes. We concluded that using this micelle delivery system for WED could improve its permeability and bioavailability to attenuate DOX-induced oxidative injury in podocytes. This study provided important information on the fact that the micelle delivery system, WED-M, showed a significant improvement of renal damage. (Copyright © 2019 Feng, Li, Wang, Li, Chen, Yang, Yang, Lian, Hou, Li, Ding and Jia.)
Databáze:	MEDLINE
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