Therapy of leishmaniasis: Superior efficacies of liposome-encapsulated drugs

Abstract

Liposomes containing antimonial compounds trapped in the aqueous phase were tested in the treatment of experimental leishmaniasis. The rationale of this approach was based on the hypothesis that the liposomes and the parasite are taken up by the same cell, the reticuloendothelial cell. EM evidence supports this hypothesis. Suppression of leishmaniasis was quantified by determining the total number of parasites per liver from impression smears. When 2 antimonials, meglumine antimoniate and sodium stibogluconate, were encapsulated within liposomes, each was more than 700 times more active compared to the free (unencapsulated) drugs. After infection, if untreated, all of the hamsters eventually would die from the disease. Liposome-encapsulated meglumine antimoniate was about 330-640 times more effective in causing a drop in the death rate than was the free antimonial. The efficacy of treatment was influenced by the lipid composition and charge of the liposomes. For example, positively charged liposomes containing egg phosphatidylcholine were much less effective than negatively charged ones. In contrast, positively and negatively charged sphingomyelin liposomes were equally effective. Liposomes containing phosphatidylserine (which were negatively charged, but also had a much higher charge density) were among the less-effective preparations. Among those tested, the most consistently efficacious liposomes contained highly saturated long-chain phospholipids (e.g., dipalmitoyl phosphatidylcholine), cholesterol and a negative charge. Liposomes may be useful as carriers of drugs to treat infectious diseases involving the RES. The toxicities of Sb are very similar to those of As. Encapsulation of antimonial drugs and reduction of the dose required for effective therapy should minimize such systemic toxicities as acute cardiomyopathy and toxic nephritis.