STABILITY OF DRY LIPOSOMES IN SUGAR GLASSES

Sugars, particularly trehalose and sucrose, are used to stabilize lipo somes during dehydration (freeze-drying and air-drying). As a result, dry liposomes are trapped in a sugar glass, a supersaturated and therm odynamically unstable solid solution, We investigated the effects of t he glassy state on liposome fusion and solute retention in the dry sta te. Solute leakage from dry liposomes was extremely slow at temperatur es below the glass transition temperature (T-g); however, it increased exponentially as temperature increased to near or above the T-g, indi cating that the glassy state had to be maintained for dry liposomes to retain trapped solutes. The leakage of solutes from dry liposomes fol lowed the law of first-order kinetics and was correlated linearly with liposome fusion. The kinetics of solute leakage showed an excellent f it with the Arrhenius equation at temperatures both above and below th e T-g, with a transitional break near the T-g. The activation energy o f solute leakage was 1320 kJ/mol at temperatures above the T-g, but in creased to 1991 kJ/mol at temperatures below the T-g. The stabilizatio n effect of sugar glass on dry liposomes may be associated with the el evated energy barrier for liposome fusion and the physical separation of dry liposomes in the glassy state. The half-life of solute retentio n in dry liposomes may be prolonged by storing dry liposomes at temper atures below the T-g and by increasing the T-g of the dry liposome pre paration.