Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery (Ministry of Education and PLA), Fudan University, Shanghai 201203, China; National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai 201203, China.
Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery (Ministry of Education and PLA), Fudan University, Shanghai 201203, China.
J Control Release. 2020 Dec 10;328:78-86. doi: 10.1016/j.jconrel.2020.08.030. Epub 2020 Aug 25.
Intravenous injection of thrombolytic drugs is the most effective strategy for the treatment of thrombotic diseases. However, the clinical application of most thrombolytic drugs is limited by hemorrhagic risks and narrow therapeutic index. The targeted drug delivery systems may help to address these problems. Inspired by the crucial role of platelets in the process of thrombus, Platelet membrane-coated PLGA cores loading lumbrokinase (PNPs/LBK) were designed for effective thrombolysis with reduced hemorrhagic risk. Using a mouse carotid thrombosis model, the affinity of platelet membrane-coated nanoparticles to the thrombus was confirmed. Also, the PNPs/LBK exhibited excellent thrombolytic efficacy at a low dose, compared with free LBK. More importantly, PNPs/LBK showed less adverse effect on the function of the coagulation system, and thus reduced hemorrhagic risk. These results indicated that a promising thrombus-targeted drug delivery system was achieved by coating PLGA nanoparticles with platelet membrane. Such rationally designed drug delivery system will provide a broad platform for thrombus treatment.
静脉注射溶栓药物是治疗血栓性疾病最有效的策略。然而，大多数溶栓药物的临床应用受到出血风险和狭窄的治疗指数的限制。靶向药物递送系统可能有助于解决这些问题。受血小板在血栓形成过程中关键作用的启发，设计了血小板膜包覆的 PLGA 核载蚓激酶（PNPs/LBK）用于有效溶栓，同时降低出血风险。使用小鼠颈动脉血栓模型证实了血小板膜包覆的纳米颗粒对血栓的亲和力。此外，与游离 LBK 相比，PNPs/LBK 在低剂量时表现出优异的溶栓效果。更重要的是，PNPs/LBK 对凝血系统功能的不良影响较小，从而降低了出血风险。这些结果表明，通过用血小板膜包覆 PLGA 纳米颗粒，实现了一种有前途的血栓靶向药物递送系统。这种合理设计的药物递送系统将为血栓治疗提供广阔的平台。
