Kongshaug M, Cheng L S, Moan J, Morgan A R
Department of Biophysics, Norwegian Radium Hospital, Oslo.
Int J Biochem Cell Biol. 1995 Jan;27(1):71-87. doi: 10.1016/1357-2725(94)00054-9.
Purpurins are potent hydrophobic photosensitizers in vivo. Cremopfore EL is an important vehicle for the administration of hydrophobic drugs. Mode-delivery-effects on the binding of etiopurpurin (ET2) to human plasma (LDL, HDL, and high density proteins, HDP) is studied for delivery in CRMaq and in DMSO by ultracentrifugation. A similar study of SnET2 is available (Kongshaug et al., 1993) and has been extended. In the absence of plasma, only nonfluorescent ET2 entities (aggregates) were present, a portion of which moved unaffected by gravity (small aggregates), the remainder according to their densities (high density aggregates). Aggregated ET2 showed, at high salt density, similar positions and halfwidths in the gradient, and similar adsorption properties as the aggregates in plasma-containing samples. In CRMaq (1 mg CRM/ml) the adsorptive loss of the dye affected only marginally the binding of fluorescent monomeric ET2. In this mode (i) 20% of ET2 was bound as monomers, about 70% of which to CRM-modified LDL, most of the remainder to CRM-modified HDL; (ii) such HDL also marginally bound small aggregates; (iii) only monomeric ET2 was bound to CRM-modified LDL. In delivery in DMSO, aggregated ET2 (98% of ET2 in the gradient) converted, post centrifugally, into minor amounts of HDL-bound monomeric ET2; LDL-bound ET2 included monomers (about 50%) and small aggregates, mainly dimers. The percentage binding of SnET2 to HDP was independent of the concentrations of CRMaq and HDL. Plasma-bound small aggregates (such as dimers) and plasma-unbound high density aggregates (mean densities of 1.13-1.19 g/ml) were substantially present in the plasma-containing samples. There were mode-delivery-effects upon the yields and properties of aggregated ET2, and upon the yields of plasma-bound monomeric ET2. Monomeric ET2 showed a remarkably high percentage binding to LDL and was similarly distributed among the lipoproteins as is total cholesterol. There was little or no real mode-delivery-effect upon the distribution of monomeric ET2 among the plasma proteins. The affinity of CRM-modified LDL for SnET2 was similar to that of HDL plus HDP in native plasma.
紫红素在体内是强效的疏水性光敏剂。聚氧乙烯蓖麻油（Cremopfore EL）是疏水性药物给药的重要载体。通过超速离心研究了在CRMaq和二甲基亚砜（DMSO）中递送时，递送方式对etiopurpurin（ET2）与人血浆（低密度脂蛋白、高密度脂蛋白和高密度蛋白，HDP）结合的影响。已有关于SnET2的类似研究（Kongshaug等人，1993年）且该研究已得到扩展。在无血浆的情况下，仅存在非荧光性的ET2实体（聚集体），其中一部分不受重力影响移动（小聚集体），其余部分根据其密度移动（高密度聚集体）。聚集的ET2在高盐密度下在梯度中显示出相似的位置和半峰宽，并且与含血浆样品中的聚集体具有相似的吸附特性。在CRMaq（1mg CRM/ml）中，染料的吸附损失仅对荧光单体ET2的结合产生轻微影响。在这种方式下：（i）20%的ET2以单体形式结合，其中约70%结合到CRM修饰的低密度脂蛋白上，其余大部分结合到CRM修饰的高密度脂蛋白上；（ii）这种高密度脂蛋白也轻微结合小聚集体；（iii）仅单体ET2结合到CRM修饰的低密度脂蛋白上。在DMSO中递送时，聚集的ET2（梯度中98%的ET2）在离心后转化为少量结合到高密度脂蛋白的单体ET2；结合到低密度脂蛋白的ET2包括单体（约50%）和小聚集体，主要是二聚体。SnET2与HDP的结合百分比与CRMaq和高密度脂蛋白的浓度无关。含血浆样品中大量存在与血浆结合的小聚集体（如二聚体）和未与血浆结合的高密度聚集体（平均密度为1.13 - 1.19g/ml）。聚集的ET2的产率和性质以及与血浆结合的单体ET2的产率存在递送方式的影响。单体ET2与低密度脂蛋白的结合百分比非常高，并且在脂蛋白中的分布与总胆固醇相似。单体ET2在血浆蛋白中的分布几乎没有或没有实际的递送方式影响。CRM修饰的低密度脂蛋白对SnET2的亲和力与天然血浆中高密度脂蛋白加HDP的亲和力相似。
