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Adv Healthc Mater. 2013 Aug;2(8):1131-41. doi: 10.1002/adhm.201200350. Epub 2013 Mar 8.

Bulk manufacture of concentrated oxygen gas-filled microparticles for intravenous oxygen delivery.

Author information

1
Department of Cardiology, Children's Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Enders 1228, Boston, Massachusetts 02115 USA. john.kheir@childrens.harvard.edu.

Abstract

Self-assembling, concentrated, lipid-based oxygen microparticles (LOMs) have been developed to administer oxygen gas when injected intravenously, preventing organ injury and death from systemic hypoxemia in animal models. Distinct from blood substitutes, LOMs are a one-way oxygen carrier designed to rescue patients who experience life-threatening hypoxemia, as caused by airway obstruction or severe lung injury. Here, we describe methods to manufacture large quantities of LOMs using an in-line, recycling, high-shear homogenizer, which can create up to 4 liters of microparticle emulsion in 10 minutes, with particles containing a median diameter of 0.93 microns and 60 volume% of gas phase. Using this process, we screen 30 combinations of commonly used excipients for their ability to form stable LOMs. LOMs composed of DSPC and cholesterol in a 1:1 molar ratio are stable for a 100 day observation period, and the number of particles exceeding 10 microns in diameter does not increase over time. When mixed with blood in vitro, LOMs fully oxygenate blood within 3.95 seconds of contact, and do not cause hemolysis or complement activation. LOMs can be manufactured in bulk by high shear homogenization, and appear to have a stability and size profile which merit further testing.

KEYWORDS:

emulsions; microcapsules; oxygen

PMID:
23471884
DOI:
10.1002/adhm.201200350
[Indexed for MEDLINE]
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