Microscopic Study of Crystal Growth in Cryopreservation Agent Solutions and Water

Liu, Tao; Hua, Tao

doi:10.1111/j.1749-6632.2002.tb04566.x

Cited by 5 publications

(1 citation statement)

References 11 publications

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“…Indeed, it has long been known that during freezing, air is released and often trapped as bubbles in the resultant ice. This phenomenon has important biological consequences in that bubble formation contributes to freezing damage in long-term preservation of cells and tissues (Carte et al 1961;Karlsson et al 1993;King et al 1974;Korber 1988;Kruuv 1985;Lipp et al 1987;Lipp et al 1994;Morris et al 1981;Steponkus et al 1981;Tao et al 2002;Toner et al 1990).…”

Section: Discussionmentioning

confidence: 99%

A Method to Co-Encapsulate Gas and Drugs in Liposomes for Ultrasound-Controlled Drug Delivery

Huang

McPherson

MacDonald

2008

Ultrasound in Medicine & Biology

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A novel method for the facile production of gas-containing liposomes with simultaneous drug encapsulation is described. Liposomes of phospholipid and cholesterol were prepared by conventional procedures of hydrating the lipid film, sonicating, freezing and thawing. A single, but critical modification of this procedure generates liposomes that contain gas (air, perfluorocarbon, argon); after sonication, the lipid is placed under pressure with the gas of interest. After equilibration, the sample is frozen. The pressure is then reduced to atmospheric and the suspension thawed. This procedure leads to entrapment of air in amounts up to 10% by volume by lipid dispersions at moderate (10mg/ml) concentrations of lipids. The amount of gas encapsulated increases with gas pressure and lipid concentration. Utilizing 0.32 M mannitol to provide an aqueous phase with physiological osmolarity, 1, 3, 6 or 9 atm of pressure was applied to 4 mg of lipid. This led to encapsulation of 10, 15, 20, and 30 l of gas in a total of 400 l of liposome dispersion (10mg lipids/ml), respectively. The mechanism for gas encapsulation presumably depends upon the fact that air (predominantly nitrogen and oxygen), like most solutes, dissolves poorly in ice and is excluded from the ice that forms during freezing. The excluded air then comes out of solution as air pockets that are stabilized in some form by a lipid coating. The presence of air in these preparations sensitizes them to ultrasound (1MHz, 8 W/cm 2 ,10 second) such that up to half of their aqueous contents (which could be a water soluble drug) can be released by short (10 s) applications of ultrasound. Both diagnostic and therapeutic applications of the method are conceivable.

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