Control of the Rate of Hepatic Uptake and Catabolism of Liposome‐Entrapped Proteins Injected into Rats. Possible Therapeutic Applications

Abstract

131 I‐ or 125 I‐labelled albumin and β‐fructofuranosidase were entrapped in liposomes composed of phosphatidylcholine, cholesterol and a charged lipid (molar ratio 7:2:1). Investigations on the fate of such liposomes injected into rats revealed the following. 1. Initially there is an increased rate of removal from plasma (rapid phase) followed by a decreased one (slow phase). The rate of removal during the rapid phase was highest for negatively charged liposomes and lowest for positively charged liposomes with neutral liposomes in between. Uniform rates of removal, regardless of charge, were obtained during the slow phase. 2. The rate of hepatic uptake of such liposomes paralleled that observed for their removal from plasma during the rapid phase. 3. Concurrent administration of a large quantity of positively charged liposomes and of a smaller quantity of negatively charged liposomes led to a diminution of the rapid phase of the latter suggesting a common site of uptake for liposomes of either charge. 4. Blockade of the reticuloendothelial system with carbon led to an increased hepatic localization of liposomes during the rapid phase suggesting a bimodal uptake of liposomes with both the Kupffer and the liver parenchymal cells involved. 5. Cross‐linking of liposome‐entrapped albumin and β‐fructofuranosidase increased the stability of the latter and following injection into rats rendered both proteins less vulnerable to degradation by the liver lysosomal enzymes. 6. The possibility of controlling both the rate of removal from plasma and catabolism of liposome‐entrapped proteins adds more scope to the use of liposomes in therapy.