Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
Int J Pharm. 2011 Feb 14;404(1-2):205-10. doi: 10.1016/j.ijpharm.2010.10.053. Epub 2010 Nov 5.
Staudinger ligation was evaluated as a strategy for synthesizing receptor targeted liposomes. First, an activated lipid derivative was synthesized by reacting dioleoyl phosphatidylethanolamine (DOPE) and 2-(diphenylphosphino) terephthalic acid 1-methyl 4-penta-fluorophenyldiester. Second, transferrin (Tf) was activated with p-azidophenyl isothiocyanate. Third, liposomes containing the activated lipid were prepared and then coupled to the activated Tf via the Staudinger reaction. These liposomes were evaluated in KB cells for cellular uptake and cytotoxicity, and in mice for pharmacokinetic properties. Tf-derivatized liposomes encapsulating calcein prepared by this conjugation method effectively targeted Tf receptor expressing KB cells. In addition, the Tf-targeted liposomes entrapping doxorubicin showed greatly enhanced in vitro cytotoxicity relative to non-targeted control liposomes. Pharmacokinetic parameters indicated that these liposomes retained long circulating properties relative to the free drug. In summary, Staudinger ligation is an effective method for the synthesis of receptor targeted liposomes.
Staudinger 连接被评估为合成受体靶向脂质体的一种策略。首先，通过反应二油酰基磷脂酰乙醇胺（DOPE）和 2-（二苯基膦）对苯二甲酸 1-甲基 4-五氟苯基二酯合成了活化脂质衍生物。其次，转铁蛋白（Tf）用对叠氮苯基异硫氰酸酯活化。第三，制备含有活化脂质的脂质体，然后通过 Staudinger 反应将其与活化的 Tf 偶联。这些脂质体在 KB 细胞中进行细胞摄取和细胞毒性评估，并在小鼠中进行药代动力学特性评估。通过这种偶联方法制备的包封 calcein 的 Tf 衍生脂质体可有效靶向表达 Tf 受体的 KB 细胞。此外，包封阿霉素的 Tf 靶向脂质体与非靶向对照脂质体相比，体外细胞毒性显著增强。药代动力学参数表明，与游离药物相比，这些脂质体保留了长循环特性。总之，Staudinger 连接是合成受体靶向脂质体的一种有效方法。
