Nacka F, Cansell M, Méléard P, Combe N
ISTAB, Nutrition et Signalisation Cellulaire, Talence, France.
Lipids. 2001 Dec;36(12):1313-20. doi: 10.1007/s11745-001-0846-x.
Liposomes made from a natural marine lipid extract and containing a high polyunsaturated n-3 fatty lipid ratio were envisaged as oral route vectors and a potential alpha-tocopherol supplement. The behavior of vesicles obtained by simple filtration and of giant vesicles prepared by electroformation was investigated in gastrointestinal-like conditions. The influence of alpha-tocopherol incorporation into liposomes was studied on both physical and chemical membrane stability. Propanal, as an oxidation product of n-3 polyunsaturated fatty acids, was quantified by static headspace gas chromatography when alpha-tocopherol incorporation into liposome ratios ranged from 0.01 to 12 mol%. Best oxidative stability was obtained for liposomes that contained 5 mol% alpha-tocopherol. Compared to the other formulas, propanal formation was reduced, and time of the oxidation induction phase was longer. Moreover, alpha-tocopherol induced both liposome structural modifications, evidenced by turbidity, and phospholipid chemical hydrolysis, quantified as the amount of lysophospholipids. This physicochemical liposome instability was even more pronounced in acid storage conditions, i.e., alpha-tocopherol incorporation into liposome membranes accelerated the structural rearrangements and increased the rate of phospholipid hydrolysis. In particular, giant vesicles incubated at pH 1.5 underwent complex irreversible shape transformations including invaginations. In parallel, the absorption rate of alpha-tocopherol was measured in lymph-cannulated rats when alpha-tocopherol was administrated, as liposome suspension or added to sardine oil, through a gastrostomy tube. Alpha-tocopherol recovery in lymph was increased by almost threefold, following liposome administration. This may be related to phospholipids that should favor alpha-tocopherol solubilization and to liposome instability in the case of a high amount of alpha-tocopherol in the membranes. A need to correlate results obtained from in vitro liposome behavior with in vivo lipid absorption was demonstrated by this study.
由天然海洋脂质提取物制成且含有高比例多不饱和n-3脂肪酸脂质的脂质体被设想为口服途径载体和潜在的α-生育酚补充剂。在类似胃肠道的条件下，研究了通过简单过滤获得的囊泡以及通过电形成制备的巨型囊泡的行为。研究了α-生育酚掺入脂质体对物理和化学膜稳定性的影响。当α-生育酚掺入脂质体的比例在0.01至12摩尔%范围内时，通过静态顶空气相色谱法定量测定作为n-3多不饱和脂肪酸氧化产物的丙醛。对于含有5摩尔%α-生育酚的脂质体，获得了最佳的氧化稳定性。与其他配方相比，丙醛的形成减少，氧化诱导期的时间更长。此外，α-生育酚诱导了脂质体的结构修饰（通过浊度证明）和磷脂化学水解（以溶血磷脂的量定量）。这种物理化学脂质体不稳定性在酸性储存条件下甚至更明显，即α-生育酚掺入脂质体膜中加速了结构重排并增加了磷脂水解速率。特别是，在pH 1.5下孵育的巨型囊泡经历了复杂的不可逆形状转变，包括内陷。同时，当通过胃造口管将α-生育酚作为脂质体悬浮液或添加到沙丁鱼油中给药时，在淋巴管插管的大鼠中测量了α-生育酚的吸收速率。脂质体给药后，淋巴中α-生育酚的回收率增加了近三倍。这可能与有利于α-生育酚溶解的磷脂以及膜中大量α-生育酚情况下的脂质体不稳定性有关。这项研究表明需要将体外脂质体行为获得的结果与体内脂质吸收相关联。
