A combinatorial approach to producing sterically stabilized (Stealth) immunoliposomal drugs
A combinatorial approach to producing sterically stabilized (Stealth) immunoliposomal drugs
复制标题
DOI：
10.1016/s0014-5793(99)01320-4
复制
发表时间：
1999-10-22
期刊：
影响因子：
3.5
通讯作者：
Allen, TM
中科院分区：
文献类型：
--
作者：
Ishida, T;Iden, DL;Allen, TM
我们已经开发了一种用于生产空间稳定的免疫脂质体药物（SIL）的方法，该方法容易适用于用于简单制造各种配体靶向脂质体药物的“混合和匹配”组合方法。偶联到由PEG-脂质衍生物（mPEG（2000）-DSPE）形成的胶束中的聚乙二醇（PEG）末端的配体可以以温度和时间依赖性的方式从胶束转移到预先形成的含药物的脂质体中。抗体密度高达100 μ g抗体/μ mol磷脂，和高达3摩尔%的mPEG（2000）-DSPE，可以同时从配体偶联胶束转移到脂质体外单层，转移过程中从脂质体的药物泄漏可忽略不计，并在人血浆中具有良好的稳定性。将抗CD 19转移到SIL中导致这些脂质体与CD 19（+）人B细胞淋巴瘤细胞的结合增加3倍。(C)1999年欧洲生物化学学会联合会。
We have developed a method for producing sterically stabilized immunoliposomal drugs (SIL) readily applicable to a 'mix and match' combinatorial approach for the simple manufacture of a variety of ligand-targeted liposomal drugs. Ligands coupled to the terminus of polyethylene glycol (PEG) in micelles formed from PEG-lipid derivatives (mPEG(2000)-DSPE) could be transferred into preformed, drug-containing liposomes from the micelles in a temperature- and time-dependent manner. Antibody densities up to 100 mu g antibody/mu mol of phospholipid, and up to 3 mol% of mPEG(2000)-DSPE, could be simultaneously transferred from the ligand-coupled micelles into the liposomal outer monolayer with negligible drug leakage from liposomes during transfer and good stability in human plasma. Transfer of anti-CD19 into SIL resulted in a three-fold increase in binding of these liposomes to CD19(+) human B cell lymphoma cells. (C) 1999 Federation of European Biochemical Societies.