Liver Liposomes

Shafaa, MW, Diehl, HA, and Socaciu, C, 2007. The solubilisation pattern of lutein, zeaxanthin, canthaxanthin and beta-carotene differ characteristically in liposomes, liver microsomes and retinal epithelial cells. Biophys Chem 129, 111-119. 

Spinazzi A, Ceriati S, Pianezzola P, Lorusso V, Luzzani F, Fouillet X, Alvino S, Rummeny EJ (2000) Safety and pharmacokinetics of a new liposomal liver-specific contrast agent for CT Results of clinical testing in nonpatient volimteers. Invest Radiol 35 1... 

Leander P, Hoglund P, Borseth A, Kloster Y, Berg A. A new liposomal liver-specific contrast agent for CT first human phase-I clinical trial assessing efficacy and safety. Eur Radiol 2001 ll(4) 698-704. 

The phagocytic potential of the liver and the spleen could be temporarily blocked by using different substances (such as rare-earth metal salts or carbon colloids). For example, injected liposome blood clearance can be reduced after MPS blockade with dextran sulfate or carbon (Souhami et al, 1981). MPS blockade was also achieved by progressively increasing intravenous (i.v.) dosages of liposomes liver saturation was first observed, followed by localization in the spleen and eventually accumulation in the bone marrow (Poste, 1983). 

Increased accumulation of liposomes, especially small liposomes, has been reported to occur at sites of inflammation (Williams et al., 1986) and in tumors (Turner et al., 1988 Gabizon and Papahadjopoulos, 1988) (cf. Sec. VI.B). However, it is well established that endo-cytosis of liposomes by MPS cells, primarily those located in liver and spleen, accounts for most of the uptake of liposomes—and, in general, uptake of particulate matter—from the blood circulation. 

One approach where the characteristics of the liposomal carrier system are well matched to the intended therapeutic application is the delivery of drugs to the MPS. Because of their particulate nature, the major route of clearance of liposomes, when administered in vivo by a variety of routes, is phagocytosis by MPS cells, especially macrophages in liver and spleen. Obviously, this "natural" fate of liposomes in vivo is an advantage if one attempts to treat diseases... 

In comparison to intravenous administration of MLV, which usually results in a rapid and almost quantitative uptake into liver and spleen, the fraction taken up into these organs is lower after intraperitoneal injection of these large liposomes. The reason might be that liposomes are trapped in lymph nodes and degradation of the liposomes in the peritoneal cavity can occur (Ellens et al., 1981 Parker et al., 1982) besides, several types of liposomes are degraded more quickly in lymphatic fluid than in plasma (Parker et al, 1981a,b). 

Changing the distribution of a drug can lead to toxic effects not described before. It is possible that after liposomal delivery high concentrations of drugs (e.g., cytotoxic drugs) inside macrophages affect these cells detrimentally (Poste and Kirsch, 1983). This results in toxic effects in liver, spleen, and bone marrow which were not previously associated with the use of these drugs. 

Peroxidation of lipids is another factor which must be considered in the safety evaluation of liposome administration. Smith and coworkers (1983) demonstrated that lipid peroxides can play an important role in liver toxicity. Allen et al. (1984) showed that liposomes protected by an antioxidant caused less MPS impairment than liposomes subjected to mild oxidizing conditions. From the study of Kunimoto et al. (1981) it can be concluded that the level of peroxidation in freshly prepared liposome preparations and those on storage strongly depends both on the phospholipid fatty acid composition and on the head group of the phospholipid. Addition of appropriate antioxidants to liposomes composed of lipids which are liable to peroxidation and designed for use in human studies is therefore necessary. 

Allen, T. M., and Smuckler, E. A. (1985). Liver pathology accompanying chronic liposome administration in mouse. Res. Commun. Chem. Pathol. Pharmacol., 50. 281-290. 

Derksen, J. T. P. (1987). Immunoglobulin-coupled liposomes and their interaction with rat liver macrophages. Ph.D. Thesis. University of Groningen, The Netherlands. 

Roerdink, F., Dijkstra, J., Hartman, G., Bolscher, B., and Scher-phof, G. L. (1981). The involvement of parenchymal, Kupffer and endothelial liver cells in the hepatic uptake of intravenously injected liposomes, Biochim. Biophys. Acta, 677, 79-89. 

Assay of lonophore Activity. Ionophoretic activities on rat liver mitochondria and liposomes were performed as described previously (72). 

Stndies of the antoxidation of carotenoids in liposomal suspensions have also been performed since liposomes can mimic the environment of carotenoids in vivo. Kim et al. stndied the antoxidation of lycopene," P-carotene," and phytofluene" " in liposomal snspensions and identified oxidative cleavage compounds. Stabilities to oxidation at room temperature of various carotenoids incorporated in pig liver microsomes have also been studied." The model took into account membrane dynamics. After 3 hr of reactions, P-carotene and lycopene had completely degraded, whereas xanthophylls tested were shown to be more stable. 

Liposomal 40 mg/m2 IV infused over 12.3%—18% Myelosuppression, stomatitis, 1. Give proper dosing for liver... 

The half-life of liposomes administered in the blood stream is affected by the composition, size, charge, and fluidity. Liposomes with a small size or with a rigid lipid bilayer have a longer half-life (38 9). Large liposomes administered iv tend to accumulate at a lymph node near the injected site. This tendency can be useful for preventing metastases. Liposomes which pass through the lymph node have a tendency to accumulate in the RES, such as the liver and spleen (40,41). The disposition of liposomes is altered by the dose of liposomes as well as size or lipid composition of liposomes. Cholesterol rich liposomes are cleared slower due to... 

Optimization of Immunoliposome Binding to the Lung. In order to reduce the uptake of immunoliposomes by the liver and spleen, we have tested the effect of incorporating GMj into the liposome membrane on the lung binding of immunoliposomes. We (74,22) and others (70,77,72) have demonstrated that the presence of this monosialoganglioside in the liposomes effectively reduces the RES uptake and prolongs the circulation time of liposomes. Since GMj contains one... 

Irrespective of size, liposomes, when injected in-traperitoneally, partially accumulate in the liver and spleen. It has been suggested that transport of liposomes from the peritoneal cavity to the systemic circulation, and eventually to tissues, occurs by lymphatic pathways. Local injection of larger liposomes leads to quantitative accumulation at the site of injection. The slow disintegration of the carrier than releases the drug, which diffuses into the blood circulation. Smaller liposomes, on the other hand, enter the lymph nodes and blood circulation and eventually accumulate in the liver and spleen. 

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