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

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  • Recent Advances in Drug Delivery
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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.

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Acknowledgments

This work made use of University of Utah shared facilities of the Micron Technology Foundation Inc. Microscopy Suite sponsored by the College of Engineering, Health Sciences Center, Office of the Vice President for Research, and the Utah Science Technology and Research (USTAR) initiative of the State of Utah.

Funding

This work was funded by the University of Utah Clinical and Translational Science Institute Pilot award program. It was supported by the University of Utah Study Design and Biostatistics Center, with funding in part from the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR002538. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Author notes

  1. Nitish Khurana and Till Sünner contributed equally to this work.

Authors and Affiliations

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

    Nitish Khurana, Venkata Yellepeddi & Hamidreza Ghandehari

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

    Till Sünner

  3. Department of Biomedical Engineering, College of Engineering, University of Utah, Salt Lake City, UT, USA

    Oliver Hubbard & Hamidreza Ghandehari

  4. Division of Clinical Pharmacology, Department of Pediatrics, School of Medicine, University of Utah, Salt Lake City, UT, USA

    Carina Imburgia, Venkata Yellepeddi & Kevin M. Watt

  5. Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA

    Gregory J. Stoddard

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  1. Nitish Khurana
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Contributions

Conceptualization: Nitish Khurana, Till Suenner, Venkata Yellepeddi, Kevin Watt, Hamidreza Ghandehari; Methodology: Nitish Khurana, Till Suenner, Oliver Hubbard, Carina Imburgia; Formal analysis: Nitish Khurana, Till Suenner, Oliver Hubbard, Gregory Stoddard; Investigation: Nitish Khurana, Till Suenner, Oliver Hubbard, Carina Imburgia; Resources: Venkata Yellepeddi, Kevin Watt, Hamidreza Ghandehari; Writing – Original Draft: Nitish Khurana; Writing – Review and editing: Nitish Khurana, Till Suenner, Oliver Hubbard, Carina Imburgia, Venkata Yellepeddi, Kevin Watt, Hamidreza Ghandehari, Gregory Stoddard; Supervision: Nitish Khurana, Venkata Yellepeddi, Kevin Watt, Hamidreza Ghandehari; Funding acquisition: Nitish Khurana, Venkata Yellepeddi, Kevin Watt, Hamidreza Ghandehari.

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Correspondence to Hamidreza Ghandehari.

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Khurana, N., Sünner, T., Hubbard, O. et al. Micellar Encapsulation of Propofol Reduces its Adsorption on Extracorporeal Membrane Oxygenator (ECMO) Circuit. AAPS J 25, 52 (2023). https://doi.org/10.1208/s12248-023-00817-2

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