Effects of positive charge density on the liposomal surface on disposition kinetics of liposomes in rats

The effects of positive charge density on the liposomal surface on the disposition kinetics of liposomes in rats were investigated. The cationic liposomes with zeta potentials of about +15 mV remained in the blood longer than did the neutral liposomes, and the hepatic uptake of these liposomes decreased. The blood clearance of the liposomes with zeta potentials under + 10 mV was comparable to that of the neutral liposomes. In contrast, the blood circulation of the liposomes with a higher positive charge density, above + 25 mV, was shortened and their hepatic uptake was almost the same as that of the neutral liposomes. The optimum value of positive charge density on the liposomal surface to prolong the residency of liposomes in the blood circulation was thus determined. A liver perfusion experiment showed that the uptake of cationic liposomes with a zeta potential of about + 15 mV was effectively suppressed in the presence of erythrocytes, while that of liposomes with a higher zeta potential were little affected. Thus, above +15 mV, the suppressive effect of erythrocytes on the hepatic uptake of cationic liposomes decreased with the increase of the positive charge on the liposomal surface. These results cannot be explained by the binding model, and we therefore propose the ionic atmosphere model: Cationic liposomes surround the erythrocytes with a negative surface charge like the ion atmosphere of the Debye-Huckel theory. The cationic liposomes with a suitable positive charge surround the erythrocytes as an ionic atmosphere and could then escape the reticuloendothelial system (RES). The higher positively charged liposomes were taken up by the liver probably due to the shield of the negative charge of erythrocytes provided by the cationic liposomal atmosphere. (C) 1997 Elsevier Science B.V.