Dynamin II（dynII）在内吞细胞的内化途径中扮演重要角色，它通过使膜凹陷形成“脱落泡”来实现这一功能。临床应用的重要类别dynII抑制剂是苯噻吩类物质，如丙氟奋（PCZ）。PCZ是一种抗精神病药物，但目前在临床试验中以更高的浓度作为癌症患者的辅助剂，用于提高高剂量静脉注射的单克隆抗体的疗效。然而，目前尚不清楚高剂量dynII抑制剂是否有可能改变通过单核吞噬细胞系统去除的共同给药的化疗纳米药物的药代动力学。因此，本研究旨在研究临床相关浓度的苯噻吩类物质PCZ和氟奋吨在体外脂质体内吞作用和PCZ静脉输注后大鼠体内脂质体药代动力学的影响。通过与dynII抑制剂共孵育，利用流式细胞仪研究了荧光标记的聚乙二醇修饰的脂质体进入分化和未分化的THP-1和RAW246.7细胞以及人体外周血细胞的摄取情况。还在大鼠中研究了在PCZ输注后，聚乙二醇修饰的脂质体的静脉药代动力学。苯噻吩类物质和dyngo4a以浓度依赖性的方式减少了THP-1和RAW264.7细胞对聚乙二醇修饰的脂质体的摄取。然而，dynII抑制剂并未改变人体外周血细胞对脂质体的平均吞噬量，但部分供体的内吞细胞对苯噻吩类物质暴露表现出敏感性。在大鼠中，当与聚乙二醇修饰的阿霉素脂质体（Caelyx/Doxil）共同给予临床相关剂量的PCZ时，脂质体的药代动力学和生物分布并未改变。这些数据表明，临床相关剂量的dynII抑制剂可以体外抑制脂质体对内吞细胞的摄取，但不太可能显著影响长循环的共同给予脂质体的药代动力学。

Dynamin II (dynII) plays a significant role in the internalization pathways of endocytic cells, by allowing membrane invaginations to "bud off". An important class of dynII inhibitors that are used clinically are phenothiazines, such as prochlorperazine (PCZ). PCZ is an antipsychotic drug but is also currently in clinical trials at higher concentrations as an adjuvant in cancer patients that increases the efficacy of monoclonal antibodies at high intravenous doses. It is unknown, however, whether high-dose dynII inhibitors have the potential to alter the pharmacokinetics of co-administered chemotherapeutic nanomedicines that are largely cleared via the mononuclear phagocyte system. This work therefore sought to investigate the impact of clinically relevant concentrations of phenothiazines, PCZ and thioridazine, on in vitro liposome endocytosis and in vivo liposome pharmacokinetics after PCZ infusion in rats. The uptake of fluorescently labeled PEGylated liposomes into differentiated and undifferentiated THP-1 and RAW246.7 cells, and primary human peripheral white blood cells, was investigated via flow cytometry after co-incubation with dynII inhibitors. The IV pharmacokinetics of PEGylated liposomes were also investigated in rats after a 20 min infusion with PCZ. Phenothiazines and dyngo4a reduced the uptake of PEGylated liposomes by THP-1 and RAW264.7 cells in a concentration-dependent manner in vitro. However, dynII inhibitors did not alter the mean uptake of liposomes by human peripheral white blood cells, but endocytic white cells from some donors exhibited sensitivity to phenothiazine exposure. When a clinically relevant dose of PCZ was co-administered with PEGylated liposomal doxorubicin (Caelyx/Doxil) in rats, the pharmacokinetics and biodistribution of liposomes were unaltered. These data suggest that while clinically relevant doses of dynII inhibitors can inhibit the uptake of liposomes by endocytic cells in vitro, they are unlikely to significantly affect the pharmacokinetics of long-circulating, co-administered liposomes.