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121.
《Journal of liposome research》2013,23(1):42-54
Liposomal vinorelbine formulation is desirable, as it might improve the therapeutic activity of vinorelbine. However, because of its lipophilic and membrane-permeable properties, vinorelbine is hard to be formulated into liposomes using conventional drug-loading technologies. To improve vinorelbine retention, ammonium salts of several anionic agents were employed to prepare liposomal vinorelbine formulations. It was found that 5-sulfosalicylate (5ssa) could form stable complexes with vinorelbine and stabilize entrapped vinorelbine. The resultant vesicles had an in vitro release t1/2 of ~12.49 hours in NH3-containing media, which is longer than those of sulfate and phytate vesicles (~0.57 hours). The circulation half-life of vinorelbine after the injection of 5ssa vesicles into normal mice was ~13.01 hours, accounting for ~2-fold increase relative to that of sulfate vesicles. Improved drug retention correlated with enhanced antitumor efficacy. In the RM-1/c57 model, 5ssa vesicles were more efficacious than sulfate vesicles (P?<?0.05). In RM-1/BDF1 and Lewis lung cancer/c57 models, antitumor efficacy was also considerably improved after vinorelbine encapsulation into 5ssa vesicles. For instance, in the RM/BDF1 model, liposomal vinorelbine was at least 4-fold more therapeutically active than free vinorelbine. Our results demonstrated that 5ssa could stabilize vinorelbine relative to other anions, resulting in the formulation with improved drug retention and efficacy. Improved vinorelbine retention might be associated with the formation of insoluble precipitate, which could be proved by precipitation study and decreased drug-release rate at a high D/L ratio. 相似文献
122.
Modulation of the Serine Base Exchange Enzyme Activity of Rat Brain Membranes by Amphiphilic Cations and Amphiphilic Anions 总被引:1,自引:0,他引:1
Abstract: The biosynthesis of phosphatidylserine in mammalian tissues is catalyzed by the serine base exchange enzyme. The activity of this membrane-bound enzyme can be manipulated by amphiphiles. Amphiphilic cations, such as oleylamine, W-7, chlorpromazine, and didodecyldimethylamine, stimulate the serine base exchange activity. Amphiphilic anions, such as bis(2-ethylhexyl) hydrogen phosphate and cholesterol sulfate, inhibit the serine base exchange activity. These effects are more pronounced at pH 7.0 than at the pH optimum of 8.5 for this enzyme. Both the stimulators and the inhibitors alter the V max values without changing the K m value for serine, suggesting that their mechanism of action is related to interactions of the membrane-bound cosubstrate, phosphatidylethanolamine, with the membrane-bound enzyme. The optimal concentration of stimulator varies with the amount of membrane protein present; however, supraoptimal concentrations cause inhibitions. It is proposed that the amphiphilic cations enhance the interaction of the phosphorylethanolamine moiety of the membrane-bound cosubstrate with the enzyme and the amphiphilic anions interfere with such an interaction. Some of the pharmacological properties of these amphiphilic cations, employed clinically as antidepressants, may be mediated by modulation of the serine base exchange enzyme activity. 相似文献
123.
M. R. Carter 《Plant and Soil》1980,56(2):293-300
Summary Iron chlorosis of 4 year old Scots pine (Pinus sylvestris L.) in comparison to areas of adjacent healthy growth on calcareous prairie soil, was associated with slight increases in the soluble ion content of the saturation paste extract. Such increases in soluble ions (mainly calcium sulphate) were associated with significant increases in ash, cation (including iron) and organic anion content of the chlorotic needles. Increasing levels of available soil nitrate were also related to increase in organic anions. Nitrogen and phosphorus assimilation was adversely affected under conditions of iron chlorosis. These observations support the theory of induced iron deficiency associated with elevated levels of organic anions or translocated cations and are applicable to plantings of conifers on prairie soils. 相似文献
124.
H. Königshofer 《Plant and Soil》1983,72(2-3):289-296
Summary The effect of salinity on the ionic balance and the hexitol content of the halophyteP. maritima L. and the nonhalophytesP. major L. ssp.major, P. lanceolata L., andP. media L. was studied in a culture experiment. In response to salt application the nonhalophilous species increased their internal electrolyte content to a considerably greater extent at high transpiration thanP. maritima. Excessive uptake of Cl and SO4 following salt-treatment was in most cases compensated by a decline in the total organic anion content in all species under investigation. Na was strongly accumulated in the shoots ofP. maritima when subjected to salt-stress, while the nonhalophytic species tended to exclude this ion from leaf tissue enhancing Mg-uptake for charge balance. Acyclic polyhydric alcohols (sorbitol and mannitol), the dominant soluble carbohydrates in allPlantago species studied, increased, with one exception, in all plants under saline conditions. The results indicate marked physiological differences between the halophyteP. maritima and the nonhalophytic members of the genusPlantago in their reaction to salinity being perhaps partially responsible for differences in the degree of salt tolerance. 相似文献