title: Manufacture of concentrated, lipid-based oxygen microbubble emulsions by high shear homogenization and serial concentration.
abstract: Gas-filled microbubbles have been developed as ultrasound contrast and drug delivery agents. Microbubbles can be produced by processing surfactants using sonication, mechanical agitation, microfluidic devices, or homogenization. Recently, lipid-based oxygen microbubbles (LOMs) have been designed to deliver oxygen intravenously during medical emergencies, reversing life-threatening hypoxemia, and preventing subsequent organ injury, cardiac arrest, and death. We present methods for scaled-up production of highly oxygenated microbubbles using a closed-loop high-shear homogenizer. The process can produce 2 L of concentrated LOMs (90% by volume) in 90 min. Resulting bubbles have a mean diameter of ~2 μm, and a rheologic profile consistent with that of blood when diluted to 60 volume %. This technique produces LOMs in high capacity and with high oxygen purity, suggesting that this technique may be useful for translational research labs.
authors.affiliation: Department of Cardiology, Boston Children's Hospital, Harvard Medical School.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Thomson
authors.affiliation: Department of Cardiology, Boston Children's Hospital, Harvard Medical School.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Polizzotti
authors.affiliation: Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, University of Pennsylvania.
authors.forename: Frances X
authors.initials: FX
authors.lastname: McGowan
authors.affiliation: Department of Cardiology, Boston Children's Hospital, Harvard Medical School; john.kheir@childrens.harvard.edu.
authors.forename: John N
authors.initials: JN
authors.lastname: Kheir
mesh_terms: D004655:Emulsions; D008055:Lipids / Q000737:chemistry*; D045423:Microbubbles; D010100:Oxygen / Q000737:chemistry*; D012212:Rheology; D033081:Shear Strength
chemical_list: D004655:Emulsions; D008055:Lipids; D010100:Oxygen