Decreased solute entrapment in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposomes prepared by freeze/thaw in the presence of physiological amounts of monovalent salts

Solute entrapment in vesicles is important fur drug delivery and gene trans fer applications. Past studies have indicated that the extent of entrapment is influenced by the salt present during the process of freeze and thaw. I n this report we show that even relatively low salt concentrations lead to a significant decrease in the entrapment yields, and we demonstrate that th is decrease is the consequence of a morphological change of the vesicle sus pension observed by cryo-transmission electron microscopy. Furthermore, mon ovalent salts present during the encapsulation process result in the format ion of a species of lipid-rich structures, whereas most vesicles remain una ffected. In addition, we compare our experimental entrapment yields with th eoretical values obtained under the assumption that the solute is uniformly dispersed inside and outside the vesicles and show that there is a relativ ely good agreement between experimental and theoretical values.