Uptake of charged liposomes by the rat liver.

The influences of liposomal surface charge on hepatic uptake of liposomes in vivo and in vitro were studied in rats. 3H-inulin was entrapped in positively charged, negatively charged or neutral liposomes composed of phosphatidylcholine, cholesterol, and a charge lipid at a molar ratio of 4:4:1, or without a charge lipid. Plasma and liver concentrations of inulin were measured 5, 15, 30, and 60 minutes after an intravenous bolus dose of liposome. The in vitro study comprised incubation of liposomes with primary culture of isolated rat hepatocytes. The incubation was terminated at 30, 60, 90, 120, and 180 minutes, and cellular uptake of inulin was determined. The results showed that the positively charged liposomes resulted in the highest plasma liposome concentration. The negatively charged liposomes gave the highest liver liposome concentration, among the three liposomes. In vitro study also demonstrated that cellular uptake of a negatively charged liposome was higher than positively charged or neutral liposomes. These results suggest that positively charged liposomes might be preferable for maintaining higher plasma concentrations, while negatively charged liposomes might be more efficient for drug delivery to the liver.