Effects of cholesterol and trehalose on the stability and phase transition behavior of freeze-dried liposomes

SATOSHI OHTAKE; CAROLINA SCHEBOR; SEAN P. PALECEK; JUAN J. DE PABLO

Water properties of food, pharmaceutical and biological materials

CRC Press -Taylor and Francis Group

Lugar: Boca Raton; Año: 2006; p. 551 - 556

The objective of the present work is to contribute to the understanding of mammalian cell membrane response to desiccation. We examine in detail the phase behavior of aqueous, frozen and freeze-dried liposomes with varying amounts of cholesterol both in the presence and absence of trehalose. The liposomes were composed of 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC), 1,2-Dipalmitoyl-sn-Glycero-3-Phosphoethanolamine (DPPE) and cholesterol in the range of 0.1 to 0.9 cholesterol/phospholipid molar ratios. The transition from a gel to a liquid crystalline phase was studied by differential scanning calorimetry and the stability of liposomes was evaluated by analyzing the retention of a fluorescent dye (calcein). Light scattering was performed to evaluate the size distribution of the liposomes before and after freezing and freeze-drying. In this work, we show partial phase diagrams of dehydrated phospholipid-cholesterol liposomes in the presence and absence of trehalose.  The liposomes show phase separation upon freeze-drying; however in the presence of trehalose, only one phase is observed.  Also, these liposomes are able to retain high percentage of encapsulated compounds when freeze-dried with trehalose.  Liposomes containing high amounts of cholesterol may be considered as a potential drug carrier alternative to pure phospholipid vesicles, given the absence of a phase transition and their high retention upon rehydration.