Formation and stability of perflubron in saline emulsions for biomedical applications: An interfacial approach.
Item
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Title
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Formation and stability of perflubron in saline emulsions for biomedical applications: An interfacial approach.
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Identifier
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AAI9510698
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identifier
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9510698
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Creator
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Oleksiak, Christian Bernard.
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Contributor
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Adviser: Henri L. Rosano
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Date
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1994
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Language
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English
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Publisher
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City University of New York.
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Subject
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Health Sciences, Pharmacy | Chemistry, Physical | Chemistry, Pharmaceutical
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Abstract
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Perflubron, a hydrophobic fluid with a high capacity for dissolving respiratory gases, can be used as an injectable temporary oxygen delivery system provided that it is emulsified, using a biocompatible emulsifier, in an aqueous solution isotonic to blood. A concentrated formulation developed by Alliance Pharmaceutical Corp. consists of perflubron droplets stabilized by a monolayer of egg yolk phospholipids (EYP), ca. 250 nm in diameter, and perflubron-free EYP vesicles. The emulsion, prepared under nitrogen atmosphere (EYP are oxidation-sensitive) and sterilized in a static autoclave for 15 minutes at 121{dollar}\sp\circ{dollar}C and 20 psi, is stable for years at positive temperatures. This uncommon stability with respect to flocculation and coalescence was studied taking a simpler, non-oxidation-sensitive, hydrogenated phospholipid (PL90H) as a model for the very complex, oxidizable, and varied EYP. It was concluded that stability for the perflubron/PL90H/saline emulsion could be achieved provided that the interfacial film is doped with a negatively charged surfactant and/or with a highly hydrated surfactant, either of which would prevent the droplets from approaching one another. These results were extended to EYP, which naturally contain both major ingredients giving rise to a very structured film at the perflubron/saline interface (phosphatidylcholine, phosphatidylethanolamine, cholesterol) and charged and/or hydrated minor ingredients that prevent flocculation and coalescence (phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, etc.). Injection trials showed that the droplets were recognized as invaders by the human immune system, which resulted in too rapid a clearance from the blood stream. It is suggested that an additive with a long hydrated moiety (ethoxylated cholesterol, CnEO) be anchored at the interface, on the assumption that the highly hydrated ethoxylated chains will wrap the droplets in a thick layer of water, making them invisible to the immune system. Perflubron/EYP-CnEO/saline emulsions are under injection trials. The theoretical importance of the interface in the formation of micro- and fine emulsions was studied concomitantly and a new mathematical model was developed emphasizing two measurable physical properties of the interface: its rigidity and the interfacial free energy.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
