Abstract：
Liposomes represent one of the most extensively studied nano-carriers due to their potential in targeted drug delivery. However, the complex in vivo fate, particularly under pathological conditions, presents challenges for clinical translation of liposomal therapeutics. Liver serves as the most important organ for liposome accumulation and metabolism. Unfortunately, the fate of liposomes under pathological liver conditions has been significantly overlooked. This study aimed to investigate the in vivo pharmacokinetic profile and biodistribution profile of liposomes under drug-induced liver injury (DILI) conditions. Two classic DILI animal models, i.e. acetaminophen-induced acute liver injury (AILI) and triptolide-induced subacute liver injury (TILI), were established to observe the effect of pathological liver conditions on the in vivo performance of liposomes. The study revealed significant changes in the in vivo fate of liposomes following DILI, including prolonged blood circulation and enhanced hepatic accumulation of liposomes. Changes in the composition of plasma proteins and mononuclear phagocyte system (MPS)-related cell subpopulations collectively led to the altered in vivo fate of liposomes under liver injury conditions. Despite liver injury, macrophages remained the primary cells responsible for liposomes uptake in liver, with the recruited monocyte-derived macrophages exhibiting enhanced ability to phagocytose liposomes under pathological conditions. These findings indicated that high capture of liposomes by the recruited hepatic macrophages not only offered potential solutions for targeted delivery, but also warned the clinical application of patients under pathological liver conditions.
摘要：
脂质体由于其在靶向药物递送中的潜力而代表最广泛研究的纳米载体之一。然而,复杂的体内命运，特别是在病理条件下，对脂质体疗法的临床翻译提出了挑战。肝脏是脂质体积累和代谢的最重要器官。不幸的是,脂质体在病理性肝脏条件下的命运已被显著忽视。本研究旨在研究药物诱导肝损伤（DILI）条件下脂质体的体内药代动力学特征和生物分布特征。两种经典的DILI动物模型，即对乙酰氨基酚诱导的急性肝损伤（AILI）和雷公藤甲素诱导的亚急性肝损伤（TILI），观察病理肝脏条件对脂质体体内性能的影响。该研究揭示了DILI后脂质体体内命运的显着变化，包括延长血液循环和增强脂质体的肝脏积累。血浆蛋白和单核吞噬细胞系统（MPS）相关细胞亚群组成的变化共同导致肝损伤条件下脂质体体内命运的改变。尽管肝损伤，巨噬细胞仍然是负责肝脏中脂质体摄取的主要细胞，招募的单核细胞衍生的巨噬细胞在病理条件下表现出增强的吞噬脂质体的能力。这些发现表明，被招募的肝巨噬细胞对脂质体的高度捕获不仅为靶向递送提供了潜在的解决方案，同时也提醒临床应用于病理性肝病患者。
