Liposome toxicity in the mouse central nervous system

Adams, David; Joyce, Greta; Richardson, V. J.; Ryman, Brenda E.; Wisniewski, H. M.

doi:10.1016/0022-510x(77)90104-6

Cited by 102 publications

(27 citation statements)

References 6 publications

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“…The toxicity of liposomes of several lipid compositions has been investigated in mice (Adams et al, 1977). Other investigators have also used liposomes containing a 7:2:1 molar ratio of egg phosphatidylcholine, cholesterol and phosphatidic acid without any observable toxic effects in rats (Gregoriadis, 1976) or man (Gregoriadis et al, 1974;Tyrrell et al, 1976;Belchetz et al, 1977).…”

mentioning

confidence: 99%

“…Other investigators have also used liposomes containing a 7:2:1 molar ratio of egg phosphatidylcholine, cholesterol and phosphatidic acid without any observable toxic effects in rats (Gregoriadis, 1976) or man (Gregoriadis et al, 1974;Tyrrell et al, 1976;Belchetz et al, 1977). However, some lipid compositions used in making liposomes have had toxic side effects (Bruni et al, 1976;Adams et al, 1977;Steger & Desnick, 1977). Animal tumour studies have shown that very small negatively charged liposomes appear to concentrate well in tumour tissue (Richardson et al, 1978a).…”

mentioning

confidence: 99%

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Tissue distribution and tumour localization of 99m-technetium-labelled liposomes in cancer patients

Richardson¹,

Ryman²,

Jewkes³

et al. 1979

Br J Cancer

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The possible use of liposomes (phospholipid vesicles) to direct cytotoxic drugs to tumours has led us to investigate the tissue localization of i.v. injected 99m-Tc-labelled liposomes in cancer patients. Twenty mg or 300 mg doses of liposomal lipid (7:2:1 molar ratio of phosphatidylcholine : cholesterol : phosphatidic acid) were used in a study of 13 patients with advanced cancer and one with polycythaemia rubra vera (PRV). In all cases except the patient with PRV the major site of uptake of the label was the liver and spleen. In the patient with PRV the liver uptake was greatly reduced and the major site of uptake was found in regions corresponding to marrow. With the exception of one patient with a primary hepatoma, there was no significant tumour uptake of the label. Images Fig. 2 Fig. 3

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confidence: 99%

mentioning

confidence: 99%

Tissue distribution and tumour localization of 99m-technetium-labelled liposomes in cancer patients

Richardson¹,

Ryman²,

Jewkes³

et al. 1979

Br J Cancer

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“…Our data on the increase in acute mortality due to the largest doses of drug in the first week of therapy (Figs. 5 (20,21) or after injection of liposomes into brain (22). In the present study, liposomes containing brain PS were among the least effective ones, whereas those containing brain SM were among the more effective (Fig.…”

Section: Influence Of Liposomalmentioning

confidence: 74%

Therapy of leishmaniasis: Superior efficacies of liposome-encapsulated drugs

Alving

Steck

Chapman

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

245

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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 lipo somes, 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.

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“…biochemical, immunological, or histopathological toxicity associated with as many as 6 injections of liposomes over a 2-wcck period 120) 1 in humans, the major consequence of RE blockade is a "spillover" phenomenon in which endotoxin (i.e.. lipid A) that would normally be detoxified by RE cells travels into other tissues and organs 19, 26. 321.…”

Section: Reticuloendothelial Blockadementioning

confidence: 99%

Liposomes as Safe Carriers of Drugs and Vaccines

Alving¹

1992

Liposome Dermatics

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Liposome toxicity in the mouse central nervous system

Cited by 102 publications

References 6 publications

Tissue distribution and tumour localization of 99m-technetium-labelled liposomes in cancer patients

Tissue distribution and tumour localization of 99m-technetium-labelled liposomes in cancer patients

Therapy of leishmaniasis: Superior efficacies of liposome-encapsulated drugs

Liposomes as Safe Carriers of Drugs and Vaccines

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