Extracorporeal membrane oxygenation (ECMO) is a life-saving cardiopulmonary bypass technology for critically ill patients with heart and lung failure. Patients treated with ECMO receive a range of drugs that are used to treat underlying diseases and critical illnesses. However, the dosing guidelines for these drugs used in ECMO patients are unclear. Mortality rate for patients on ECMO exceeds 40% partly due to inaccurate dosing information, caused in part by the adsorption of drugs in the ECMO circuit and its components. These drugs range in hydrophobicity, electrostatic interactions, and pharmacokinetics. Propofol is commonly administered to ECMO patients and is known to have high adsorption rates to the circuit components due to its hydrophobicity. To reduce adsorption onto the circuit components, we used micellar block copolymers (Poloxamer 188 and Poloxamer 407) and liposomes tethered with poly(ethylene glycol) to encapsulate propofol, provide a hydrophilic shell and prevent its adsorption. Size, polydispersity index (PDI), and zeta potential of the delivery systems were characterized by dynamic light scattering, and encapsulation efficiency was characterized using High Performance Liquid Chromatography (HPLC). All delivery systems used demonstrated colloidal stability at physiological conditions for seven days, cytocompatibility with a human leukemia monocytic cell line, i.e., THP-1 cells, and did not activate the complement pathway in human plasma. We demonstrated a significant reduction in adsorption of propofol in an ECMO model upon encapsulation in micelles and liposomes. These results show promise in reducing the adsorption of hydrophobic drugs to the ECMO circuits by encapsulation in nanoscale structures tethered with hydrophilic polymers on the surface.

中文翻译：

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减少体外膜氧合模型中疏水性药物的吸附

体外膜肺氧合（ECMO）是一种针对心肺衰竭危重患者的救生体外循环技术。接受 ECMO 治疗的患者会接受一系列用于治疗基础疾病和危重疾病的药物。然而，这些药物用于 ECMO 患者的剂量指南尚不清楚。 ECMO 患者的死亡率超过 40%，部分原因是剂量信息不准确，部分原因是 ECMO 回路及其组件中药物的吸附造成的。这些药物涉及疏水性、静电相互作用和药代动力学。异丙酚通常用于 ECMO 患者，并且由于其疏水性而对回路组件具有较高的吸附率。为了减少对电路元件的吸附，我们使用胶束嵌段共聚物（泊洛沙姆 188 和泊洛沙姆 407）和聚乙二醇束缚的脂质体来封装异丙酚，提供亲水外壳并防止其吸附。通过动态光散射表征递送系统的尺寸、多分散指数 (PDI) 和 zeta 电位，并使用高效液相色谱 (HPLC) 表征封装效率。使用的所有递送系统均在生理条件下表现出7天的胶体稳定性、与人白血病单核细胞系（即THP-1细胞）的细胞相容性，并且不激活人血浆中的补体途径。我们证明，在 ECMO 模型中，封装在胶束和脂质体中后，异丙酚的吸附显着减少。这些结果表明，通过将疏水性药物封装在表面与亲水性聚合物相连的纳米级结构中，有望减少疏水性药物对 ECMO 回路的吸附。