Studies on the kinetics of uptake and distribution of free and liposome-entrapped primaquine, and of sporozoites by isolated perfused rat liver.

The kinetics of uptake and the distribution of free primaquine differed markedly from that of liposome-entrapped primaquine. The uptake of the liposome-entrapped drug (LPQ) was gradual, reaching a plateau of 60% of the initial load after 20 minutes of perfusion. However, clearance of the free drug was almost immediate, reaching its maximum uptake of 44% within five minutes. Some interactions also seen between liposomes and malarial sporozoites. In mixed perfusions the removal of LPQ was enhanced whilst the uptake of sporozoites remained normal. Liposome uptake was significantly lower in livers obtained from silica-treated animals, in which Küpffer cell numbers are depleted. Further, analysis of the radioactive content of hepatocyte and Küpffer cell fractions following perfusion with 3H and 14C labelled liposomes suggested that the vesicles were concentrated in the latter cell type.