el-Gamal B A, Pfliegler G, Crawford N
Department of Biochemistry and Cell Biology, Hunterian Institute, Royal College of Surgeons of England, London, United Kingdom.
Thromb Haemost. 1992 Nov 10;68(5):606-14.
A novel approach to site-directed delivery of drugs in vivo using blood platelets as carrier vehicles is being investigated. In this context some initial studies are reported on the effect of platelet encapsulated anti-platelet drugs on platelet aggregation and adhesion to fibrillar collagen and injured arteries in vitro. The stable prostacyclin analogue Iloprost has been encapsulated within human and pig platelets by high voltage electroporation (Hughes and Crawford 1989 and 1990). After resealing the platelets, the packaged drug has a negligible effect upon platelet adhesion to a surface of fibrillar collagen or to damaged aorta (stripped to the tunica media to simulate deep injury). The rate of platelet recruitment to the collagen shows no dose dependency with respect to intracellular Iloprost concentrations. After high Iloprost loading, as few as 2% drug loaded platelets in a mixture with control (sham encapsulated) platelets, inhibit agonist-induced platelet aggregation > 50%. The prior deposition of a "lawn" of Iloprost-loaded platelets onto fibrillar collagen or damaged aorta has a substantial inhibitory effect (50-70%) upon the secondary recruitment of normal platelets compared with recruitment to a "lawn" of normal platelets. This inhibition of secondary recruitment occurs even in the presence of a platelet activator. If reduction of platelet recruitment to a vessel wall lesion results in a decrease in the local concentration of platelet granule-derived smooth muscle cell chemotactic and proliferative factors, this site-directed drug delivery may well have application for the prevention of restenosis following balloon angioplasty procedures.
一种利用血小板作为载体在体内进行药物定点递送的新方法正在研究中。在此背景下，报道了一些关于血小板包裹抗血小板药物对体外血小板聚集以及对纤维状胶原蛋白和受损动脉的黏附作用的初步研究。通过高压电穿孔法（休斯和克劳福德，1989年和1990年）已将稳定的前列环素类似物伊洛前列素包裹于人及猪的血小板内。重新封闭血小板后，包裹的药物对血小板黏附于纤维状胶原蛋白表面或受损主动脉（剥离至中膜以模拟深部损伤）的影响可忽略不计。血小板募集至胶原蛋白的速率与细胞内伊洛前列素浓度无关。在高剂量伊洛前列素负载后，在与对照（假包裹）血小板的混合物中，仅2%负载药物的血小板就能抑制激动剂诱导的血小板聚集达50%以上。与募集至正常血小板“草坪”相比，预先在纤维状胶原蛋白或受损主动脉上沉积伊洛前列素负载的血小板“草坪”对正常血小板的二次募集具有显著的抑制作用（50 - 70%）。即使存在血小板激活剂，这种二次募集的抑制作用依然会发生。如果减少血小板向血管壁损伤部位的募集会导致血小板颗粒衍生的平滑肌细胞趋化和增殖因子的局部浓度降低，那么这种定点药物递送很可能可用于预防球囊血管成形术后的再狭窄。
