| Autor: |
Liang Feng, Zhi-yong Li, Long Wang, Xing-hua Li, Ya-ping Chen, Bing Yang, Dang Yang, Yuan-pei Lian, Xue-feng Hou, Jun-hui Li, Shu-min Ding, Xiao-bin Jia |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Frontiers in Bioengineering and Biotechnology, Vol 7 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2296-4185 |
| DOI: |
10.3389/fbioe.2019.00333 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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