College of Pharmacy
81 Biocompatibility of Micellar and Liposomal Formulations of Hydrophobic Drugs for use with Extracorporeal Membrane Oxygenation (ECMO) Circuits
Jane Staples; Nitish Khurana; Kamiya Watkins; Debika Ghatak; Venkata Yellepeddi; Kevin Watt; and Hamidreza Ghandehari
Faculty Mentor: Nitish Khurana (Pharmaceutics & Pharmaceutical Chemistry, University of Utah)
Extracorporeal membrane oxygenation (ECMO) is a cardiopulmonary bypass device used for critically ill patients with refractory heart and lung failure. Although the technology is lifesaving, dosing information for ECMO supported patients is highly variable. Dosing can differ for ECMO patients because the ECMO circuit components can adsorb the drugs, resulting in suboptimal drug exposure. Hydrophobic drugs are extremely vulnerable to getting adsorbed on the ECMO circuits, due to interaction of hydrophobic drugs with hydrophobic surfaces of ECMO circuit components. Micellar or liposomal encapsulation of the drug can reduce adsorption. The hydrophobic drug is packaged within the hydrophilic shell so that hydrophobic interactions with ECMO circuit components are minimized. The goal of this study was to optimize micelle and liposomal formulations of the hydrophobic drugs propofol, a common anesthetic, and furosemide, a diuretic and test their biocompatibility. Propofol and furosemide were encapsulated in triblock copolymers forming micelles: Kolliphor® P 407 Geismar (P407 MP) or Kolliphor® P 188 Geismar (P188 MP), as well as the following lipids to form liposomes (LP): Dipalmitoylphosphatidylcholine(DPPC), cholesterol, and PEG 2000. Size and polydispersity (PDI) were characterized using Dynamic Light Scattering. Cytocompatibility and hemocompatibility of the formulations were analyzed in human macrophages and human plasma, respectively. Size and low PDI of P407 propofol (25nm; 0.007), P188 propofol (27nm; 0.243), liposomal propofol (141nm; 0.200), P407 furosemide (11nm; 0.020), P188 furosemide (4nm; 0.040), and liposomal furosemide (85nm; 0.200) demonstrated low polydispersity. All formulations were cytocompatible and hemocompatible. These formulations can be tested in an ex-vivo ECMO for their adsorption profile.
