THE EFFECT OF BLOOD-SERUM ON THE SIZE AND STABILITY OF PHOSPHOLIPID LIPOSOMES

Liposomes have been prepared by sonication (SUV) and reverse phase evaporation (REV) from dipalmitoylphosphatidylcholine (DPPC) and its mixtures with phosphatidylinositol (PI), stearylamine and cholesterol. The effect of rat and human blood serum on the liposomes has been investigated by measurement of the particle size in the serum-liposome mixtures by photon correlation spectroscopy in the range of serum protein concentration up to approx. 25 mg ml-1. At low serum protein concentrations the measured particle sizes exceed those calculated from the known sizes and concentrations of liposomes and serum particles in the mixtures: a result consistent with serum-induced aggregation of the liposomes, but the aggregates dissociate at higher serum protein concentration. The effect of serum on the release of encapsulated [C-14]glucose from REV liposomes has been investigated over a range of serum protein concentration by gel filtration. At low serum concentration a proportion of the liposomes remain intact but as the serum concentration is increased the size of the liposomes decreases with concomitant release of encapsulated glucose. At high serum concentrations (approx. 24 mg protein per ml) the larger liposomes in the distribution are disrupted and some of the liposomal lipid becomes associated with serum protein. The results are discussed with reference to the effect of blood on the uptake of liposomes by rat liver.