Huang Zhaohua, Guo Xin, Li Weijun, MacKay J Andrew, Szoka Francis C
Department of Biopharmaceutical Sciences, University of California-San Francisco, San Francisco, CA 94143-0446, USA.
J Am Chem Soc. 2006 Jan 11;128(1):60-1. doi: 10.1021/ja057024w.
The use of pH-sensitive liposomes for acid-triggered site-specific drug delivery is one of the more promising approaches to improve the therapeutic index of drugs. Here, we report the synthesis, assembly, and hydrolysis of the first ortho ester phosphocholine (OEPC). The acid hydrolysis of OEPC liposomes consists of a lag phase and a burst phase. The lag time is pH-dependent-the lower the pH, the shorter the time. Upon acid hydrolysis, the OEPC liposomes were transformed into leaky metastable vesicles that rapidly collapsed in the presence of albumin. OEPC, when formulated with cationic lipid, significantly enhanced the transfection efficiency compared with that of the pH-insensitive formulation.
使用pH敏感脂质体进行酸触发的位点特异性药物递送是提高药物治疗指数的更有前景的方法之一。在此,我们报道了首个原酸酯磷酸胆碱(OEPC)的合成、组装及水解过程。OEPC脂质体的酸水解包括一个延迟期和一个爆发期。延迟时间取决于pH值——pH值越低,时间越短。酸水解后,OEPC脂质体转变为有泄漏的亚稳囊泡,在白蛋白存在下会迅速塌陷。与pH不敏感制剂相比,当与阳离子脂质一起配制时,OEPC显著提高了转染效率。