Influence of lipid composition and ionic strength on the physical stability of liposomes.

The effect of including charge-inducing agents (stearylamine or phosphatidylserine) on the zeta potential of phosphatidylcholine-cholesterol-containing liposomes in aqueous media with varying ionic strength (sodium chloride) was investigated. In 150 mM ionic strength solutions, the experimentally obtained zeta potentials were in good agreement with predictions made with the Gouy-Chapman equation, after proper correction for bulk ionic interaction. However, at low ionic strength, substantial deviations occurred which were ascribed to incomplete dissociation of the phosphatidylserine molecules or protonation of the stearylamine molecules due to the large diffuse double layer (Debye length). Predictions were made on the physical stability of the liposomes based on the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory and current knowledge of hydration effects on interparticle interaction. For negatively charged liposomes, both at low and high ionic strength, no increase in particle size was found after storage. For low ionic strength solutions, this agreed with the calculations; for the high ionic strength solutions, aggregate formation in a secondary minimum was expected. For positively charged liposomes, the physical stability predicted from theoretical considerations did not correlate with the experimentally observed stability.