Liposomes In Liver Research Articles

Tissue distribution of galactosyl daphnoretin liposomes in rats

To study the tissue distribution of galactosyl daphnoretin liposomes in rats. At the dose of 10 mg•kg⁻¹, daphnoretin solution, daphnoretin liposomes, and galactosyl daphnoretin liposomes were administered to healthy SD rats via tail vein injection. The blood and tissue of heart, liver, spleen, lung, kidney, stomach, small intestine, brain and thymus were collected at 5, 15, 30, 45, 60, 120, 240, 360 min after administration. The concentrations of daphnoretin in plasma and tissue samples were determined by HPLC. The results showed that galactosyl daphnoretin liposomes group had the highest concentration of daphnoretin in liver of unit weight at different time points; and at all of the time points, the target index DTI values of galactosyl daphnoretin liposomes to liver were greater than that of daphnoretin liposomes. Compared with daphnoretin solution, the AUC0-6 and Cmax of galactosyl daphnoretin liposomes in liver were 2.23, 5.22 times, respectively. This indicated that galactosyl daphnoretin liposomes can be concentrated at liver, with a significant liver targeting effect.

Binding patterns of peptide-containing liposomes in liver and spleen of developing mice: comparison with heparan sulfate immunoreactivity

Background: Liposomes incorporating peptide from the Plasmodium circumsporozoite protein (CSP) accumulate rapidly and selectively in adult mouse liver.Purpose: The development of the liposome-binding pattern in liver and spleen was studied in relationship to the development of extracellular matrix molecules.Methods: Liposomes were administered to mice intravascularly or applied to the surface of liver and spleen slices in vitro. Slices were analyzed immunocytochemically.Results: Liposomes were found along sinusoidal borders of liver, including the basolateral border of hepatocytes. The pattern was detected in the youngest animals studied (newborn). Intensity of heparan sulfate immunoreactivity increased until adult levels were reached at 20 days. Immunoreactivity for heparan sulfate proteoglycan, but not other proteoglycans, was detected in the youngest animals, and mimicked the pattern of liposome binding. The pattern of liposome binding in the spleen, concentrated in marginal zones, was similar to the pattern of heparan sulfate immunoreactivity, and also similar to the distribution of macrophage immunoreactivity.Conclusion: The postnatal development of liposome binding parallels the development of heparan sulfate immunoreactivity, supporting the suggestion that peptide-containing liposomes target liver by binding to heparan sulfate proteoglycans. Specific delivery of liposomes by targeting heparan sulfate proteoglycans is an effective strategy even at early time periods.

リポソーム膜中のコレステロール含量が及ぼす補体第３成分（Ｃ３）の結合と体内動態への影響

In this study we analyzed the binding ability of complement component 3 (C3) associated with liposomes after incubation in rat serum in order to determine the effect of cholesterol content of liposomes on the complement system liposomes interactions and the fate of liposomes in vivo. Liposomes having different cholesterol content showed no difference in clearances from blood circulation, while in both hepatic and renal clearances the liposomes showed marked difference. The hepatic clearance increased with increasing cholesterol content and the renal clearance decreased with increasing cholesterol content. Further, it appeared that those liposomes had different C3 binding potentials : cholesterol-rich (44 mol%) liposomes had higher affinity for C3 than cholesterol-poor (22 mol%) liposomes. Interestingly, there was a good correlation between the C3 binding ability and hepatic clearance of liposomes, while there was an inverse correlation between the C3 binding ability and renal clearance of liposomes. These results suggested that the extent of interaction of liposomes with complement system directly related to the distribution of liposomes in liver, leading to a possibility that the liposomes having high affinity for C3 are phagocytosed by Kuppfer cells via complement receptors. Release of encapsulated carboxy fluorescein from liposomes was inhibited in heat-treated rat serum, less done in EDTA-treated one. This finding indicated that degradation of liposomes in in vivo or in vitro was attributed to a heat-labile serum component, but not complement system. We clarified in this study that the complement-liposome interactions play a critical role on the hepatic uptake of liposomes, but not on the degradation of liposomes in blood circulation.

Evaluation of dipalmitoylphosphatidylcholine liposomes containing a soybean-derived sterylglucoside mixture for liver targeting.

We investigated multilamellar vesicle (MLV) liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and a soybean-derived sterylglucoside mixture (SG) (DPPC/SG-liposomes) for targeting liver parenchymal cells after administration via the tail vein in mice, using liposome-entrapping calcein. The accumulation of DPPC/SG(7:2, mole ratio, DPPC:SG = 7:2)-liposomes in the liver was the highest among DPPC/SG-liposomes. About 80% and 40% of the dose of DPPC/SG(7:2)-liposomes accumulated in the liver at 15 min and 2 h, respectively, but about 20% of DPPC/SG(7:3.5, 7:7)-liposomes accumulated at 2 h after an intravenous administration. However, the uptake of DPPC/SG(7:2, 7:3.5, 7:7)-liposomes by liver parenchymal cells was about 7 times greater than that in non-parenchymal cells irrespective of the SG concentration in liposomes. The uptake of DPPC/SG(7:2)-liposomes in liver was almost the same level as that by liposomes containing lactocylceramide (LC) (LC-liposomes) that were already known to be taken up in liver parenchymal cells by the asialoglycoprotein receptor. DPPC/SG(7:2)-liposomes effectively targeted liver, having optimal stability and SG.

Tissue distribution of liposomes prepared from synthetic amphiphiles after intraperitoneal injection into mice

The tissue distribution of 99mTc-labeled vesicles prepared from synthetic amphiphiles containing an amino acid residue (synthetic liposomes) after intraperitoneal (i.p.) injection in Ehrlich solid tumor-bearing mice was investigated. Synthetic liposomes were labeled with 99mTc using stearylamine-diethylenetriaminepentaacetic acid as a chelator. The accumulation of the synthetic liposomes in liver decreased and that in pancreas significantly increased in comparison with those after intravenous injection. Gamma camera images after i.p. injection also indicated high uptake of the synthetic liposomes in pancreas. The radioactivity of the synthetic liposomes in vitro was taken up most highly in pancreas among some excised organs.

The presence of G M1 in liposomes with entrapped doxorubicin does not prevent RES blockade

The incorporation of ganglioside G M1 or phosphatidylethanolamine-polyethyleneglycol conjugates into liposomes can result in extended circulation lifetimes in vivo. This has been attributed to an ability to avoid uptake by the reticuloendothelial system (RES), specifically the phagocytic cells of the liver and spleen. Here we examine whether a representative large unilamellar vesicle (LUV) formulation which contains G M1 (distearoylphosphatidylcholine/cholesterol/G M1, 45:45:10 mol/mol), actually does avoid the RES. It is shown that a pre-dose of LUVs which contain G M1 and entrapped doxorubicin blocks the accumulation of subsequently injected empty distearoylphosphatidylcholine/cholesterol liposomes in liver. It is therefore concluded that liposomes exhibiting extended circulation lifetimes can induce RES blockade and do not avoid uptake by liver phagocytes.

Effects of liposome size on the degradation of bovine brain sphingomyelin/cholesterol liposomes in the mouse liver

The relative rates of degradation of the outer lipid bilayer of large multilamellar and small unilamellar bovine brain sphingomyelin/cholesterol ( 2:1; mol/mol) liposomes in the livers of Balb/c mice were compared. The rate of the release of entrapped In-111 ions from the aqueous reservoir of small unilamellar liposomes or from the outermost aqueous compartment of multilamellar liposomes was used to monitor the rate of degradation of the exterior lipid bilayer surface of these liposomes. The technique of gamma-ray perturbed angular correlation and a method for loading In-111 ions into the outermost aqueous compartment of liposomes were used in this investigation. It was found that in the liver the exterior lipid bilayer of large multilamellar liposomes was degraded more rapidly than the bilayer of small unilamellar liposomes in vivo. In contrast to the situation for small unilamellar liposomes, the degradative process for large multilamellar liposomes in the liver was not maintained under ischemic conditions. Our results suggest that multiple pathways operate in the degradation of liposomes in the liver. The rate of degradation of liposomes in the liver may depend on accessibility of liposomes to degradative sites.

Preferential Localization of Radiolabeled Liposomes in Liver

Liposome formulations were studied to achieve an efficient entrapment procedure for the production of liposomes of 99mTc-pentetic acid. The entrapment efficiency was studied by separation of the product using column chromatography. The particle-size range of the prepared liposomes was evaluated using electron microscopy. Entrapment techniques and separation procedures led to a liposome preparation with particles in the colloidal size range (0.001–0.5 pm). Dramatic differences in the organ distribution of the liposome preparation in mice were pro-duced when different particle-size ranges were injected. Liposomes eluted in the first fraction after the void volume led to a maximum uptake by the liver and spleen 10 min after intravenous injection. Liposomes from pooled fractions provided less than half of the activity in the liver, as did the narrow size range liposome preparation.