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 cati onic liposomes with zeta potentials of about +15 mV remained in the bl ood longer than did the neutral liposomes, and the hepatic uptake of t hese liposomes decreased. The blood clearance of the liposomes with ze ta potentials under + 10 mV was comparable to that of the neutral lipo somes. In contrast, the blood circulation of the liposomes with a high er positive charge density, above + 25 mV, was shortened and their hep atic uptake was almost the same as that of the neutral liposomes. The optimum value of positive charge density on the liposomal surface to p rolong the residency of liposomes in the blood circulation was thus de termined. A liver perfusion experiment showed that the uptake of catio nic liposomes with a zeta potential of about + 15 mV was effectively s uppressed in the presence of erythrocytes, while that of liposomes wit h a higher zeta potential were little affected. Thus, above +15 mV, th e suppressive effect of erythrocytes on the hepatic uptake of cationic liposomes decreased with the increase of the positive charge on the l iposomal surface. These results cannot be explained by the binding mod el, and we therefore propose the ionic atmosphere model: Cationic lipo somes surround the erythrocytes with a negative surface charge like th e ion atmosphere of the Debye-Huckel theory. The cationic liposomes wi th a suitable positive charge surround the erythrocytes as an ionic at mosphere and could then escape the reticuloendothelial system (RES). T he higher positively charged liposomes were taken up by the liver prob ably due to the shield of the negative charge of erythrocytes provided by the cationic liposomal atmosphere. (C) 1997 Elsevier Science B.V.