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胶束包载丙泊酚减少其在体外膜肺氧合(ECMO)回路中的吸附。

Micellar Encapsulation of Propofol Reduces its Adsorption on Extracorporeal Membrane Oxygenator (ECMO) Circuit.

机构信息

Utah Center for Nanomedicine, Department of Molecular Pharmaceutics, College of Pharmacy, University of Utah, Salt Lake City, UT, USA.

Philipps Universität Marburg, Institut für Pharmazeutische Technologie und Biopharmazie, Marburg, Germany.

出版信息

AAPS J. 2023 May 25;25(4):52. doi: 10.1208/s12248-023-00817-2.

Abstract

Extracorporeal membrane oxygenation (ECMO) is a life-saving cardiopulmonary bypass device used on critically ill patients with refractory heart and lung failure. Patients supported with ECMO receive numerous drugs to treat critical illnesses and the underlying diseases. Unfortunately, most drugs prescribed to patients on ECMO lack accurate dosing information. Dosing can be variable in this patient population because the ECMO circuit components can adsorb drugs and affect drug exposure substantially. Propofol is a widely used anesthetic in ECMO patients and is known to have high adsorption rates in ECMO circuits due to its high hydrophobicity. In an attempt to reduce adsorption, we encapsulated propofol with Poloxamer 407 (Polyethylene-Polypropylene Glycol). Size and polydispersity index (PDI) were characterized using dynamic light scattering. Encapsulation efficiency was analyzed using High performance liquid chromatography. Cytocompatibility of micelles was analyzed against human macrophages and the formulation was finally injected in an ex-vivo ECMO circuit to determine the adsorption of propofol. Size and PDI of micellar propofol were 25.5 ± 0.8 nm and 0.08 ± 0.01, respectively. Encapsulation efficiency of the drug was 96.1 ± 1.3%. Micellar propofol demonstrated colloidal stability at physiological temperature for a period of 7 days, and was cytocompatible with human macrophages. Micellar propofol demonstrated a significant reduction in adsorption of propofol in the ECMO circuit at earlier time points compared to free propofol (Diprivan®). We observed 97 ± 2% recovery of the propofol from the micellar formulation after an infusion. These results demonstrate the potential of micellar propofol to reduce drug adsorption to ECMO circuit.

摘要

体外膜肺氧合 (ECMO) 是一种用于治疗心肺衰竭的危重病患者的救命心肺转流设备。接受 ECMO 支持的患者接受了许多治疗危急疾病和潜在疾病的药物。不幸的是,大多数为 ECMO 患者开具的药物缺乏准确的剂量信息。由于 ECMO 回路组件可以吸附药物并显著影响药物暴露,因此该患者人群的剂量可能会有所不同。丙泊酚是 ECMO 患者中广泛使用的麻醉剂,由于其高疏水性,已知在 ECMO 回路中有很高的吸附率。为了减少吸附,我们用泊洛沙姆 407 (聚乙二醇-聚丙二醇) 包裹丙泊酚。使用动态光散射法对其粒径和多分散指数 (PDI) 进行了表征。使用高效液相色谱法分析了包封效率。将胶束与人巨噬细胞进行细胞相容性分析,最后将制剂注入体外 ECMO 回路中,以确定丙泊酚的吸附情况。胶束丙泊酚的粒径和 PDI 分别为 25.5±0.8nm 和 0.08±0.01。药物的包封效率为 96.1±1.3%。胶束丙泊酚在生理温度下具有 7 天的胶体稳定性,并且与人类巨噬细胞具有细胞相容性。与游离丙泊酚 (Diprivan®) 相比,胶束丙泊酚在 ECMO 回路中更早时间点显示出丙泊酚吸附的显著减少。我们观察到在输注后从胶束制剂中回收了 97±2%的丙泊酚。这些结果表明,胶束丙泊酚具有减少药物吸附到 ECMO 回路的潜力。

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