2197-63-9Relevant academic research and scientific papers
Liposomal polyamine-dialkyl phosphate conjugates as effective gene carriers: Chemical structure, morphology, and gene transfer activity
Dewa, Takehisa,Asai, Tomohiro,Tsunoda, Yuka,Kato, Kiyoshi,Baba, Daisuke,Uchida, Misa,Sumino, Ayumi,Niwata, Kayoko,Umemoto, Takuya,Iida, Kouji,Oku, Naoto,Nango, Mamoru
, p. 844 - 852 (2010)
Synthetic cationic lipids are promising transfection agents for gene therapy. We report here that polyamine conjugates of dialkyl phosphates, combined with natural lipids and assembled in the form of liposomes (polycationic liposome: PCL), possess high transfection activity in the COS-1 cell line. Furthermore, we describe the functional morphology of the PCL/DNA complexes as revealed by atomic force microscopy (AFM). The conjugates were synthesized from dialkyl phosphates (with alkyl chain lengths of 12, 14, or 16 carbons) by reaction with the polyamine molecules, spermidine, spermine, or polyethylenimine (PEI(1800)). [Dewa, T., et al. Bioconjugate Chem. 2004, 15, 824]. The PCL composed of the spermidine and C16 conjugate combined with phospholipid and cholesterol (conjugate/phospholipid/cholesterol = 1/1/1 as a molar ratio) exhibited 3.6 times higher activity than that of a popular commercial product. Systematic tests revealed clear correlations of the transgene activity with physical properties of the polyamine, in particular, that longer alkyl chains and the lower molecular weight polyamines (spermidine, spermine) favor high efficacy at the higher nitrogen/phosphate ratio = 24 (N/P, stoichiometric ratio of nitrogen in the conjugate to phosphate in DNA). The low molecular weight polyamine-based PCLs, which formed 150-400 nm particles with plasmid DNA (lipoplexes), exhibited ～3-fold higher gene transfer activity than micellar aggregates (lacking phospholipid and cholesterol) of the corresponding conjugate. In contrast, the PEI-based PCL formed large aggregates (～1 μm), that, like the micellar aggregate form, had low activity. Activity of the low molecular weight polyamine-based PCLs increased linearly with the N/P of the lipoplex up to N/P = 24. Formation of lipoplexes was examined by agarose gel electrophoresis, dynamic light scattering (DLS), and AFM. At the lower N/P = 5, large aggregates of complex (～1 μm), in which DNA molecules were loosely packed, were observed. At higher N/P, lipoplexes were converted into smaller particles (150-400 nm) having a lamellar structure, in which DNA molecules were tightly packed. Such morphological features of the lipoplex correlate with the dependence of transfection on the N/P in that the lamellar structures gave superior transfection. AFM also indicated that the lipoplexes disassembled significantly, releasing DNA, when the lipoplexes were exposed to acidic conditions (pH 4). The significance for transfection activity of the metamorphosis of bilayer lipoplexes is discussed relative to that of the less active micellar aggregate form, which is unresponsive to pH change.
Alkyl chain length dependency in hydrolysis of liposomal phosphatidylcholine by dialkylphosphate
Hayashi,Arakane,Naito,Nagano,Hirobe
, p. 1751 - 1754 (1995)
Because an amphiphile with a positive or negative charge, such as dialkylphosphate or stearylamine, is often added to liposomal phosphatidylcholine (PC) dispersions to prevent aggregation of the liposomes, we investigated the long-term stability of liposomes prepared from saturated PC in the presence of various amphiphiles. On storage of these liposomes at 40°C, PC was gradually hydrolyzed by dialkylphosphate, a negatively charged lipid, while neither stearylamine, a positively charged lipid, nor a non- charged lipid hydrolyzed PC at all. This hydrolysis of PC was examined using dialkylphosphates of various alkyl chain lengths (C10, C12, C14, C16, C18 and C20) and PC with different fatty acyl chain lengths (C14, C16 and C18). The rate of hydrolysis was maximum when the alkyl chain length of dialkylphosphate was almost equal to the fatty acyl chain length of PC. That is, the hydrolysis of dimyristoyl (C14) and dipalmitoyl (C16) acyl chains of PC was accelerated most by the incorporation of dimyristylphosphate (C14) and dipalmitylphosphate (C16), respectively. Distearoyl (C18) acyl chains of PC were hydrolyzed effectively by the incorporation of distearylphosphate (C18) as well as dipalmitylphosphate (C16). The hydrolysis did not occur when methyl dipalmitylphosphate was added instead of dipalmitylphosphate, or when the liposomal structure was decomposed by adding ethanol. These results suggest that dialkylphosphate and PC are aligned head to tail in liposomes and that the phosphate functional group causes the hydrolysis of the esters of PC. The incorporation of cholesterol into PC bilayers suppressed the hydrolysis of PC above the phase transition temperature (T(c)) of PC, but increased it below the T(c). The hydrolysis of PC by dialkylphosphate appears to depend on membrane fluidity and to be accelerated with increased membrane fluidity, because cholesterol reduces the fluidity of the liposomal membrane above the T(c) and enhances it below the T(c).
GELLED HYDROCARBONS FOR OILFIELD PROCESSES, PHOSPHATE ESTER COMPOUNDS USEFUL IN GELLATION OF HYDROCARBONS AND METHODS FOR PRODUCTION AND USE THEREOF
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Page/Page column 8, (2011/04/14)
Phosphate esters useful for gelling hydrocarbons in combination with a metal source are disclosed along with methods of preparation of the phosphate esters. Fouling in oil refinery towers has been attributed due to distillation of impurities present in phosphate esters used to gel hydrocarbons for oil well fracturing. The improved method of preparation of the phosphate ester results in a product that substantially reduces or eliminates volatile phosphorus, which is phosphorus impurities that distill up to 250° C., and increases the high temperature viscosity of the hydrocarbon gels formed using the phosphate esters.
POLYCATIONIZED PHOSPHOLIPID DERIVATIVES
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Page/Page column 18, (2010/04/30)
The present invention provides novel phospholipid derivatives. Furthermore, the present invention provides lipid membrane structures excellent in gene/nucleic acid introduction efficiency into a cell.
