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

Abstract

I3'I-or '251-labelled albumin and B-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 B-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 liposomeentrapped proteins adds more scope to the use of liposomes in therapy.

Combination Therapy Using Sodium Antimony Gluconate in Stearylamine-Bearing Liposomes against Established and Chronic Leishmania donovani Infection in BALB/c Mice

“…There are considerable discrepancies in ideas as to how charges affect the interaction of liposomes with macrophages and their distribution in vivo. In contrast to previous observations (16,20,24), there are increasing reports of improved delivery of drug-entrapped positively charged liposomes to the liver as well as the spleen over the results seen with neutral and negatively charged vesicles (3,18) and of better uptake by macrophages (27,30) and efficient parasite clearance. The efficacies of most antileishmanials, including SAG, depend on the duration of infection, and the effect is more evident in the spleen than the liver (4,26).…”

Lipoplex-induced hemagglutination: potential involvement in intravenous gene delivery

“…Much is known about how size, lamellarity, and lipid composition affect plasma pharmacokinetics and biodistribution of liposomes. 21,23,24 Cationic liposomes containing stearylamine 25 or aminoglycolipids 26 were shown to be accumulated in the liver and spleen after i.v. injection.…”

Is half‐life of circulating liposomes determined by changes in their permeability?

“…For instance, efficient interaction of drug-containing liposomes with target cells in the intravascular space or access to extravascular cells is likely to be promoted by the carrier's prolonged presence in the circulation. To this end, there has been variable success through reduction of vesicle size [2], adjustment of surface charge [3], or phospholipid composition [4,5], the use of phospholipase-resistant phospholipids [6] and, indirectly, by blocking the reticuloendothelial system [3,7,8]. However, an important prerequisite for retarded liposome clearance is resistance to the detrimental effect of blood on bilayer stability 19,101.…”