Liposils: An effective strategy for stabilizing Paclitaxel loaded liposomes by surface coating with silica
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The effect of E coli endotoxin on the leakage of 14C-sucrose from phosphatidylcholine liposomes in the absence or presence of Ca2+ was studied. Endotoxin decreased the leakage from liposomes from 27% to 4% in 5 hr when Ca2+ (1 mM) was incorporated into liposomes during sonication. The effect of endotoxin on the leakiness of liposomes was concentration dependent. Ca2+ alone increased the leakage of 14C-sucrose from liposomes. Mg2+ at concentrations higher than 5 mM exhibited an effect similar to that of Ca2+. These findings suggest that endotoxin increases the molecular packing of phosphatidylcholine bilayers in the presence of Ca2+ or Mg2+. A change in the physical state of membrane lipid bilayers induced by endotoxin may affect the function of biological membranes.
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Leakage (economics)
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Liposomes composed of egg phosphatidylcholine (PC) and cholesterol (Chol), of which ratios (PCIChol) were 111, 1/O.6, 1/O.2 were prepared, and the stabilities of these iiposomes in the blood circulation were studied by the double fluorescent labeling method described in the previous report.i) As the result, it was proved that the liposome composed of 1/1 ratio of PCIChol was stable enough, but with decreasing Chol contents of liposoomes, entrapped materials were leaked from iiposomes. The result obtained in this study was in accordance with the previous reports2'3) and double fiuorescent labeling methodi) has been found very useful for the study on liposomes.
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The uptake mechanisms of liposomes by rat peritoneal macrophages (PMs) were investigated. Incubation of liposomes with fresh rat serum enhanced the uptake of liposomes depending on the liposome size and cholesterol (CH) content. The binding of liposomes was also enhanced by serum, and this increase depended on the size and CH content as in the case of liposome uptake, which suggested that the binding of opsonized liposomes with PMs govern the extent in liposome uptake. The rate constant for the internalization (kint) was calculated by measuring both uptake and binding. The kint cannot explain the variation of liposome uptake for different sizes and CH contents. The kint values for liposomes with high (44%) and medium (33%) CH contents were constant (2.5-1), while those for liposomes with low (22%) Ch content were significantly elevated (5-9h-1). These results indicate the persence of at least two kinds of uptake mechanisms of liposomes. Treatment of serum with anti-C3 antiobdy completly inhibited the enhanced uptake of CH-high, large liposomes, which suggested that complement receptor-mediated phagocytosis may be an uptake mechanism for CH-high and -medium liposomes. In addition, complement-independent enhanced uptake was suggested for CH-low liposomes, since no inhibition was observed for CH-low liposomes by anti-C3 antibody and these liposomes were disintegrated in serum via complement-independent pathway. These results provided evidence that PMs take up liposomes via complement-dependent and indepenedent mechanisms depending on the CH content of the liposomes.
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AbstractThe immune response to HSA-phosphatidylcholine complexes administered to rabbits was not markedly enhanced when compared with the response to unmodified ESA.It was found in earlier work that HSA entrapped in liposomes (mainly composed of phosphatidylcholine) evoked a strong immune response under conditions where no response was detected to free HSA.The present results exclude the possibility that HSA- phosphatidylcholine complexes which may arise from liposome- encapsulated HSA may be responsible for the adjuvant activity of the liposomes.The adjuvant activity of liposomes could also be established after administration of a liposome-associated strong antigen (BGG).
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瞄准：由于源于先进胃的癌症的腹膜炎 carcinomatosa 与腹水在病人在它的静脉内的管理以后在血浆和腹水检验 paclitaxel 集中。方法：有腹水的二个病人在这研究由于源于胃的癌症的腹膜炎 carcinomatosa 被包括。在血浆和腹水的 paclitaxel 集中为 72 h 被调查以防 1 和 168 h 以防 2 在静脉内的管理以后。结果：在血浆的 paclitaxel 集中在管理以后立即达到顶点，在 24 h 以内在 0.1 微摩尔(85 ng/mL ) 的阀值价值下面由快速的减少列在后面。相反，在腹水的 paclitaxel 集中在管理以后为 24 h 逐渐地增加了到与在血浆发现的水平一致的水平。在 24 h 以后，在腹水和血浆的 paclitaxel 的水平变得类似，与被维持直到 72 h 追随者管理的最佳的水平。结论：在腹水的 paclitaxel 的集中在静脉内的管理以后为多达 72 h 为癌症房间的治疗在最佳的水平以内被维持。Paclitaxel 是为胃的癌症的恶意的腹水的治疗的有希望的药。
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Ethylenediaminetetraacetic acid
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Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study, we have analyzed the interaction the sodium diclofenac (SD) with soya phosphaditylcholine (PC) and soya phosphatidylcholine from lyophilized small unilamellar liposomes (SUV). The changes in the properties of the co-lyophilized drug/PC from SUV liposomes, lyophilized PC from SUV liposomes, and lyophilized soya phosphatidylcholine, were studied by Differential Scanning Calorimetry (DSC). The DSC data showed that the previous organization of phospholipids molecules to form liposome affects intensely the thermal behavior of PC when compared to non-lipossomal PC. SD modified the thermal properties of PC from liposomes. It was verified that SD affects intensely the located group peaks in the regions of 120-140 ºC and in the higher temperature region of 240-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-liposomal PC and that these modifications can be easily monitored by DSC analysis.
Diclofenac Sodium
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We previously reported that liposomes composed of phosphatidylethanolamine (PE) and fatty acid exhibited pH-dependent leakage, aggregation and fusion (N. Hazemoto, M. Harada, N. Komatubara, M. Haga and Y. Kato, Chem. Pharm. Bull., 38, 748 (1990)). In this study, we have examined the effects of phosphatidylcholine (PC) and cholesterol (Chol) on the pH-sensitivity of liposomes. Contents-leakage from liposomes was always accompanied by a change in light-scattering, suggesting that aggregation or fusion of liposomes causes the leakage. The pH-sensitivity was observed only when liposomes contained less than 32 mol% of PC. The leakage vs. pH curves shifted to the more acidic regions as the PC content of the liposomes increased, but the maximum leakage (%) did not change. The effect of cholesterol on the pH-sensitivity depended on the PC/PE ratio of the liposomes. Addition of cholesterol to PC/PE/oleic acid (OA) liposomes system induced two effects, that is, aggregation of liposomes via the reduction in PC content and the stabilization of the liposomal membrane. It was shown that pH-sensitivity can be controlled by addition of the appropriate amount of PC and/or Chol to liposomal lipids.
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