NDLI: Therapy of leishmaniasis: superior efficacies of liposome-encapsulated drugs.

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Therapy of leishmaniasis: superior efficacies of liposome-encapsulated drugs.

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Therapy of leishmaniasis: superior efficacies of liposome-encapsulated drugs.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Steck, E. A. Chapman, W. L. Alving, C. R. Hendricks, L. D. Waits, V. B. Swartz, G. M. Hanson, W. L.
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, and we present electron microscopic evidence that supports this hypothesis. Suppression of leishmaniasis was quantified by determining the total number of parasites per liver from impression smears. When two antimonials, meglumine antimoniate and sodium stibogluconate, were encapsulated within liposomes, each was more than 700 times more active compared to either of 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 (eg., dipalmitoyl phosphatidylcholine), cholesterol, and a negative charge. We conclude that liposomes may be useful as carriers of drugs to treat infectious diseases involving the reticuloendothelial system. The toxicities of antimony are very similar to those of arsenic. Encapsulation of antimonial drugs and reduction of the dose required for effective therapy should minimize such systemic toxicities as acute cardiomyopathy and toxic nephritis.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	6
Volume Number	75
Language	English
Publisher	National Academy of Sciences
Publisher Date	1978-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antimony Sodium Gluconate Administration & Dosage Antimony Disease Models, Animal Gluconates Leishmaniasis Drug Therapy Liposomes Therapeutic Use Pharmaceutical Vehicles Animals Cricetinae Parasitology Liver Meglumine Analogs & Derivatives Phospholipids Structure-Activity Relationship Surface Properties Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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