Interactions of polymerizable phosphatidylcholine vesicles with blood components: relevance to biocompatibility.
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.
D001672:Biocompatible Materials; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000378:metabolism*; D010314:Partial Thromboplastin Time; D010713:Phosphatidylcholines; D010974:Platelet Aggregation; D011108:Polymers; D011517:Prothrombin Time
D001672:Biocompatible Materials; D001798:Blood Proteins; D008081:Liposomes; D010713:Phosphatidylcholines; D011108:Polymers; C052762:1,2-bis(1,2-(lipoyl)dodecanoyl)-sn-glycero-3-phosphocholine; C044273:bis(1,2-(methacryloyloxy)dodecanoyl)phosphatidylcholine; D005337:Fibrin