Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT, USA; Utah Center for Nanomedicine, University of Utah, Salt Lake City, UT, USA; Division of Clinical Pharmacology, Department of Pediatrics, School of Medicine, University of Utah, Salt Lake City, UT, USA.
Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT, USA; Utah Center for Nanomedicine, University of Utah, Salt Lake City, UT, USA.
Eur J Pharm Biopharm. 2024 May;198:114261. doi: 10.1016/j.ejpb.2024.114261. Epub 2024 Mar 14.
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 in-vitro 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.
体外膜肺氧合（ECMO）是一种治疗心肺衰竭重症患者的救生心肺转流技术。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病的药物。然而，ECMO 患者使用的这些药物的剂量指南尚不清楚。部分原因是由于剂量信息不准确，导致 ECMO 患者的死亡率超过 40%，部分原因是药物在 ECMO 回路及其组件中的吸附。这些药物在疏水性、静电相互作用和药代动力学方面存在差异。丙泊酚常用于 ECMO 患者，由于其疏水性，已知其对回路组件有很高的吸附率。为了减少对回路组件的吸附，我们使用胶束嵌段共聚物（泊洛沙姆 188 和泊洛沙姆 407）和与聚乙二醇连接的脂质体来包裹丙泊酚，提供亲水性外壳并防止其吸附。通过动态光散射对输送系统的粒径、多分散指数（PDI）和 zeta 电位进行了表征，通过高效液相色谱（HPLC）对包封效率进行了表征。所有输送系统在生理条件下的七天内均表现出胶体稳定性，与人类白血病单核细胞系，即 THP-1 细胞具有细胞相容性，并且不会在人血浆中激活补体途径。我们在体外 ECMO 模型中证明，在包裹在胶束和脂质体中后，丙泊酚的吸附显著减少。这些结果表明，通过在纳米结构上用表面连接的亲水性聚合物进行封装，可以减少疏水性药物对 ECMO 回路的吸附。
