School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, People's Republic of China.
Nanjing Jiangning District Hospital of Traditional Chinese Medicine, Nanjing 211100, People's Republic of China.
Int J Nanomedicine. 2020 Feb 17;15:1101-1115. doi: 10.2147/IJN.S235832. eCollection 2020.
The clinical use of doxorubicin (DOX) is severely limited due to its cardiotoxicity. Thus, there is a need for prophylactic and treatment strategies against DOX-induced cardiotoxicity.
The purpose of this study was to develop a liquiritigenin-loaded submicron emulsion (Lq-SE) with enhanced oral bioavailability and to explore its efficacy against DOX-induced cardiotoxicity.
Lq-SE was prepared using high-pressure homogenization and characterized using several analytical techniques. The formulation was optimized by central composite design response surface methodology (CCD-RSM). In vivo pharmacokinetic studies, biochemical analyses, reactive oxygen species (ROS) assays, histopathologic assays, and Western blot analyses were performed.
Each Lq-SE droplet had a mean particle size of 221.7 ± 5.80 nm, a polydispersity index (PDI) of 0.106 ± 0.068 and a zeta potential of -28.23 ± 0.42 mV. The area under the curve (AUC) of Lq-SE was 595% higher than that of liquiritigenin (Lq). Lq-SE decreased the release of serum cardiac enzymes and ameliorated histopathological changes in the hearts of DOX-challenged mice. Lq-SE significantly reduced oxidative stress by adjusting the levels of ROS, increasing the activity of antioxidative enzymes and inhibiting the protein expression of NOX4 and NOX2. Furthermore, Lq-SE significantly improved the inflammatory response through the mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) signalling pathway and induced cardiomyocyte apoptosis.
Lq-SE could be used as an effective cardioprotective agent against DOX in chemotherapy to enable better treatment outcomes.
由于阿霉素（DOX）的心脏毒性，其临床应用受到严重限制。因此，需要针对 DOX 诱导的心脏毒性制定预防和治疗策略。
本研究旨在开发一种具有增强口服生物利用度的甘草素负载亚微米乳剂（Lq-SE），并探讨其对抗 DOX 诱导的心脏毒性的疗效。
采用高压均质法制备 Lq-SE，并采用多种分析技术进行表征。通过中心复合设计响应面法（CCD-RSM）对配方进行优化。进行了体内药代动力学研究、生化分析、活性氧（ROS）测定、组织病理学检测和 Western blot 分析。
每个 Lq-SE 液滴的平均粒径为 221.7 ± 5.80nm，多分散指数（PDI）为 0.106 ± 0.068，zeta 电位为-28.23 ± 0.42mV。Lq-SE 的曲线下面积（AUC）比甘草素（Lq）高 595%。Lq-SE 降低了血清心脏酶的释放，并改善了 DOX 挑战的小鼠心脏的组织病理学变化。Lq-SE 通过调节 ROS 水平、增加抗氧化酶活性和抑制 NOX4 和 NOX2 的蛋白表达，显著减轻氧化应激。此外，Lq-SE 通过丝裂原激活蛋白激酶（MAPK）/核因子-κB（NF-κB）信号通路显著改善了炎症反应，并诱导心肌细胞凋亡。
Lq-SE 可用作化疗中对抗 DOX 的有效心脏保护剂，以实现更好的治疗效果。
