State Key Laboratory of Natural Medicine, The School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China.
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore.
ACS Appl Mater Interfaces. 2022 Aug 31;14(34):38562-38574. doi: 10.1021/acsami.2c11117. Epub 2022 Aug 16.
Cardioprotective medication is the common treatment to relieve myocardial ischemia/reperfusion (I/R) injury. However, limited by the low bioavailability of therapeutic drugs, the therapeutic outcome is barely satisfactory. Because the I/R injury can enhance the permeability of the vasculature and allow the extravasation of nanoparticles into the surrounding tissue, herein we formulate the cardiotonic drug olprinone (Olp) in cross-linked micelles as the nanomedicine to achieve myocardium-targeted delivery after systematic administration. As a result, the local concentration of Olp in the injured myocardium is raised by orders of magnitude with prolonged drug duration time. The treatment successfully preserves the pumping efficiency of the heart, alleviates ventricular remodeling, and thus stops the positive feedback loop for the deteriorated cardiac function. Consequently, the myocardium-targeted nanomedicine significantly salvages the heart from I/R injury before irreversible pathological changes take place.
心脏保护药物是缓解心肌缺血/再灌注（I/R）损伤的常用治疗方法。然而，由于治疗药物的生物利用度低，治疗效果并不理想。由于 I/R 损伤可增强血管通透性，并使纳米颗粒外渗到周围组织中，因此我们将心脏收缩药物奥拉西坦（Olp）制成交联胶束作为纳米药物，在系统给药后实现心肌靶向递送。结果，局部 Olp 浓度在损伤心肌中提高了几个数量级，药物持续时间延长。该治疗方法成功地保持了心脏的泵血效率，减轻了心室重构，从而阻止了心脏功能恶化的正反馈循环。因此，在不可逆的病理变化发生之前，心肌靶向纳米药物可显著拯救心脏免受 I/R 损伤。
