Romberg Birgit, Metselaar Josbert M, Baranyi Lajos, Snel Cor J, Bünger Rolf, Hennink Wim E, Szebeni Janos, Storm Gert
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands.
Int J Pharm. 2007 Mar 1;331(2):186-9. doi: 10.1016/j.ijpharm.2006.11.018. Epub 2006 Nov 11.
Poly(amino acid)s (PAAs) were evaluated as coating polymers for long-circulating liposomes. The pharmacokinetics of PAA-coated liposomes were assessed in rats. Prolonged circulation times were obtained, comparable to those reported for poly(ethylene glycol) (PEG)-liposomes. Besides, the enzymatic degradability of PAAs was studied. PAAs - in free as well as liposome-associated form - are degradable by proteases, which is beneficial for reducing the risks of accumulation in vivo. Furthermore, complement activation by PAA-liposomes was evaluated in vitro and in vivo. Like other liposome types, they appear to activate the complement system. However, a role of endotoxin contamination of the PAA-liposome formulations used cannot be excluded in our complement activation studies.
聚氨基酸（PAAs）被评估为用于长循环脂质体的包衣聚合物。在大鼠中评估了聚氨基酸包衣脂质体的药代动力学。获得了延长的循环时间，与聚乙二醇（PEG）脂质体报道的循环时间相当。此外，还研究了聚氨基酸的酶促降解性。游离形式以及与脂质体相关形式的聚氨基酸都可被蛋白酶降解，这有利于降低体内蓄积风险。此外，还在体外和体内评估了聚氨基酸脂质体的补体激活情况。与其他类型的脂质体一样，它们似乎会激活补体系统。然而，在我们的补体激活研究中，不能排除所用聚氨基酸脂质体制剂内毒素污染的作用。
