Hildebrand Annegret, Beyer Katja, Neubert Reinhard, Garidel Patrick, Blume Alfred
Martin-Luther-University Halle-Wittenberg, Institute of Pharmaceutical Technology and Biopharmaceutics, Wolfgang-Langenbeck-Str. 4, D-06120 Halle/Saale, Germany.
J Colloid Interface Sci. 2004 Nov 15;279(2):559-71. doi: 10.1016/j.jcis.2004.06.085.
The interactions of the bile salts sodium cholate (NaC) and sodium deoxycholate (NaDC) in 0.1 M NaCl (pH 7.4) with membranes composed of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), 1,2-dipalmitoyl-sn-glycero-3-phosphatidylglycerol (DPPG) and mixtures of DPPC and DPPG at molar ratios of 3:1 and 1:1 were studied by means of high-sensitivity isothermal titration calorimetry (ITC), dynamic light scattering (DLS), and differential scanning calorimetry (DSC). The partition coefficients and the transfer enthalpies for the incorporation of bile salt molecules into the phospholipid membranes were determined by ITC. The vesicle-to-micelle transition was investigated by ITC, DLS, and DSC. The phase boundaries for the saturation of the vesicles and their complete solubilization established by ITC were in general agreement with DLS data, but systematic differences could be seen due to the difference in detected physical quantities. Electrostatic repulsion effects between the negatively charged bile salt molecules and the negatively charged membrane surfaces are not limiting factors for the vesicle-to-micelle transition. The membrane packing constraints of the phospholipid molecules and the associated spontaneous curvature of the vesicles play the dominant role. DPPG vesicles are transformed by the bile salts into mixed micelles more easily or similarly compared to DPPC vesicles. The saturation of mixed DPPC/DPPG vesicles requires less bile salt, but to induce the solubilization of the liposomes, significantly higher amounts of bile salt are needed compared to the concentrations required for the solubilization of the pure phospholipid systems. The different solubilization behavior of DPPC/DPPG liposomes compared to the pure liposomes could be due to a specific "extraction" of DPPG into the mixed micelles in the coexistence region.
通过高灵敏度等温滴定量热法（ITC）、动态光散射法（DLS）和差示扫描量热法（DSC），研究了在0.1 M NaCl（pH 7.4）中胆盐胆酸钠（NaC）和脱氧胆酸钠（NaDC）与由1,2-二棕榈酰-sn-甘油-3-磷酸胆碱（DPPC）、1,2-二棕榈酰-sn-甘油-3-磷酸甘油（DPPG）以及摩尔比为3:1和1:1的DPPC与DPPG混合物组成的膜之间的相互作用。通过ITC测定了胆盐分子掺入磷脂膜的分配系数和转移焓。通过ITC、DLS和DSC研究了囊泡到胶束的转变。ITC确定的囊泡饱和及其完全溶解的相边界与DLS数据总体一致，但由于检测的物理量不同，可以看到系统差异。带负电荷的胆盐分子与带负电荷的膜表面之间的静电排斥效应不是囊泡到胶束转变的限制因素。磷脂分子的膜堆积限制和囊泡相关的自发曲率起主导作用。与DPPC囊泡相比，DPPG囊泡更容易或同样容易地被胆盐转化为混合胶束。混合的DPPC/DPPG囊泡的饱和需要较少的胆盐，但与纯磷脂体系溶解所需的浓度相比，诱导脂质体溶解需要显著更多的胆盐。与纯脂质体相比，DPPC/DPPG脂质体不同的溶解行为可能是由于在共存区域DPPG被特异性“萃取”到混合胶束中。
