Bonté F, Hsu M J, Papp A, Wu K, Regen S L, Juliano R L
Biochim Biophys Acta. 1987 Jun 12;900(1):1-9. doi: 10.1016/0005-2736(87)90271-9.
We have studied the biocompatibility properties of polymerizable phosphatidylcholine bilayer membranes, in the form of liposomes, with a view toward the eventual utilization of such polymerized lipid assemblies in drug carrier systems or as surface coatings for biomaterials. The SH-based polymerizable lipid 1,2-bis[1,2-(lipoyl)dodecanoyl]-sn-glycero-3-phosphocholine (dilipoyl lipid, DLL) and the methacryl-based lipid 1,2-bis[(methacryloyloxy)dodecanoyl]-sn-glycero-3-phosphocholine (dipolymerizable lipid, DPL) were studied in comparison to 'conventional' zwitterionic or charged phospholipids. We examined binding of serum proteins to liposomes and effects of liposomes on fibrin clot formation and on platelet aggregation. All types of liposomes tested bound complex mixtures of serum proteins with IgG being the most abundant bound component. DPL vesicles and anionic vesicles bound substantially more protein than other vesicle types. Polymerized DPL vesicles uniquely bound a protein of about 53 kDa which was not bound to other types of phosphatidylcholine liposomes. Likewise polymerized DPL vesicles, but not other types of phosphatidylcholine vesicles, caused a marked alteration in coagulation as measured by activated partial thromboplastin time (APTT) and prothrombin time (PT) tests; this effect was shown to be due to binding and depletion of clothing factor V by the DPL polymerized vesicles. Polymerized DPL liposomes and DLL liposomes in polymerized or nonpolymerized form, were without substantial effect on platelet aggregation. However, DPL nonpolymerized vesicles, while not causing aggregation, did impair ADP-induced aggregation of platelets. These studies suggest that SH based polymerizable lipids of the DLL type may be very suitable for in vivo use in the contexts of drug delivery systems or biomaterials development. Methacryloyl-based lipids of the DPL type seem to display interactions with the hemostatic process which militate against their in vivo utilization.
我们研究了脂质体形式的可聚合磷脂酰胆碱双层膜的生物相容性特性，以期最终将此类聚合脂质组装体用于药物载体系统或作为生物材料的表面涂层。将基于SH的可聚合脂质1,2-双[1,2-(硫辛酰基)十二烷酰基]-sn-甘油-3-磷酸胆碱（二硫辛酰基脂质，DLL）和基于甲基丙烯酸酯的脂质1,2-双[(甲基丙烯酰氧基)十二烷酰基]-sn-甘油-3-磷酸胆碱（双可聚合脂质，DPL）与“传统”两性离子或带电磷脂进行了比较研究。我们检测了血清蛋白与脂质体的结合以及脂质体对纤维蛋白凝块形成和血小板聚集的影响。所有测试的脂质体类型均结合血清蛋白的复杂混合物，其中IgG是结合最丰富的成分。DPL囊泡和阴离子囊泡比其他囊泡类型结合的蛋白要多得多。聚合的DPL囊泡独特地结合了一种约53 kDa的蛋白，该蛋白不与其他类型的磷脂酰胆碱脂质体结合。同样，聚合的DPL囊泡，而非其他类型的磷脂酰胆碱囊泡，通过活化部分凝血活酶时间（APTT）和凝血酶原时间（PT）测试显示出凝血方面的显著改变；这种效应被证明是由于DPL聚合囊泡结合并消耗了凝血因子V。聚合的DPL脂质体和聚合或未聚合形式的DLL脂质体对血小板聚集没有实质性影响。然而，未聚合的DPL囊泡虽然不会引起聚集，但确实会损害ADP诱导的血小板聚集。这些研究表明，DLL类型的基于SH的可聚合脂质可能非常适合在药物递送系统或生物材料开发的背景下用于体内。DPL类型的基于甲基丙烯酸酯的脂质似乎表现出与止血过程的相互作用，这不利于它们在体内的应用。
