Meyenburg S, Lilie H, Panzner S, Rudolph R
Institut für Biotechnologie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle/Saale, Germany.
J Control Release. 2000 Oct 3;69(1):159-68. doi: 10.1016/s0168-3659(00)00295-9.
The efficacy of biologically active proteins in medical therapy depends on the development of suitable drug delivery systems. These delivery systems need to overcome the severe problems connected with the use of proteins such as their usually short half lives in body fluids and their susceptibility to proteolysis and denaturation. Our delivery system combines two widespread devices by encapsulating liposomes containing the model protein horseradish peroxidase (HRP) inside the biopolymer fibrin. The liposomes enable the protein to remain in its preferred aqueous environment and protect it during the polymerization process. Further encapsulation of the liposomes inside fibrin was carried out in order to achieve a depot system with sustained protein release. In vitro experiments showed that the protein filled liposomes were absolutely stable within the fibrin network. In contrast to 'free' HRP, enzyme entrapped in liposomes was completely retained by the fibrin network and wasn't released from the device unless the fibrin was degraded by plasmin.
生物活性蛋白在医学治疗中的疗效取决于合适药物递送系统的开发。这些递送系统需要克服与蛋白质使用相关的严重问题,例如它们在体液中通常较短的半衰期以及对蛋白水解和变性的敏感性。我们的递送系统通过将含有模型蛋白辣根过氧化物酶(HRP)的脂质体包裹在生物聚合物纤维蛋白内,结合了两种广泛使用的装置。脂质体使蛋白质能够保持在其优选的水性环境中,并在聚合过程中保护它。为了实现具有持续蛋白质释放的储库系统,进一步将脂质体包裹在纤维蛋白内。体外实验表明,填充蛋白质的脂质体在纤维蛋白网络内绝对稳定。与“游离”HRP相比,包裹在脂质体中的酶被纤维蛋白网络完全保留,除非纤维蛋白被纤溶酶降解,否则不会从装置中释放出来。