Delivery of a mitochondria‐targeted antioxidant from biocompatible, polymeric nanofibrous scaffolds,FEBS Open Bio

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Delivery of a mitochondria‐targeted antioxidant from biocompatible, polymeric nanofibrous scaffolds
FEBS Open Bio ( IF 2.8 ) Pub Date : 2020-11-11 , DOI: 10.1002/2211-5463.13032
Yasaman Hamedani ₁ , Rayane Brinck Teixeira ₂ , Catherine Karbasiafshar ₂ , Peter Wipf _{3,

4,

5} , Sankha Bhowmick ₁ , M Ruhul Abid ₂

Affiliation

Cardiovascular disease has been associated with increased levels of reactive oxygen species (ROS). Recently, we have shown that a critical balance between cytosolic ROS and mitochondrial ROS is crucial in cardiovascular health and that modulation of mitochondrial ROS helps prevent detrimental effects of cytosolic ROS on endothelial cells (EC) in transgenic animals. Here, we report the development of a controlled delivery system for a mitochondria‐targeted antioxidant, JP4‐039, from an electrospun scaffold made of FDA‐approved biocompatible polymeric nanofibers. We demonstrate that the active antioxidant moiety was preserved in released JP4‐039 for over 72 h using electron paramagnetic resonance. We also show that both the initial burst release of the drug within the first 20 min and the ensuing slow and sustained release that occurred over the next 24 h improved tube formation in human coronary artery ECs (HCAEC) in vitro. Taken together, these findings suggest that electrospinning methods can be used to upload mitochondrial antioxidant (JP4‐039) onto a biocompatible nanofibrous PLGA scaffold, and the uploaded drug (JP4‐039) retains nitroxide antioxidant properties upon release from the scaffold, which in turn can reduce mitochondrial ROS and improve EC function in vitro.

中文翻译：

从生物相容性聚合物纳米纤维支架递送靶向线粒体的抗氧化剂

心血管疾病与活性氧 (ROS) 水平升高有关。最近，我们已经证明细胞溶质 ROS 和线粒体 ROS 之间的关键平衡对心血管健康至关重要，线粒体 ROS 的调节有助于防止细胞溶质 ROS 对转基因动物内皮细胞 (EC) 的有害影响。在这里，我们报告了线粒体靶向抗氧化剂 JP4-039 的控制递送系统的开发，该系统来自由 FDA 批准的生物相容性聚合物纳米纤维制成的电纺支架。我们证明，使用电子顺磁共振，活性抗氧化剂部分在释放的 JP4-039 中保存超过 72 小时。体外。综上所述，这些发现表明，静电纺丝方法可用于将线粒体抗氧化剂 (JP4-039) 加载到生物相容性纳米纤维 PLGA 支架上，并且加载的药物 (JP4-039) 在从支架释放后保留了氮氧化合物的抗氧化特性，这反过来又体外可降低线粒体ROS，改善EC功能。

更新日期：2021-01-04

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