Gabizon Alberto A, Shmeeda Hilary, Zalipsky Samuel
Shaare Zedek Medical Center, Hebrew University Medical School, Jerusalem, Israel.
J Liposome Res. 2006;16(3):175-83. doi: 10.1080/08982100600848769.
Coating of liposomes with polyethylene-glycol (PEG) by incorporation in the liposome bilayer of PEG-derivatized lipids results in inhibition of liposome uptake by the reticulo-endothelial system and significant prolongation of liposome residence time in the blood stream. Parallel developments in drug loading technology have improved the efficiency and stability of drug entrapment in liposomes, particularly with regard to cationic amphiphiles such as anthracyclines. An example of this new generation of liposomes is a formulation of pegylated liposomal doxorubicin known as Doxil or Caelyx, whose clinical pharmacokinetic profile is characterized by slow plasma clearance and small volume of distribution. A hallmark of these long-circulating liposomal drug carriers is their enhanced accumulation in tumors. The mechanism underlying this passive targeting effect is the phenomenon known as enhanced permeability and retention (EPR) which has been described in a broad variety of experimental tumor types. Further to the passive targeting effect, the liposome drug delivery platform offers the possibility of grafting tumor-specific ligands on the liposome membrane for active targeting to tumor cells, and potentially intracellular drug delivery. The pros and cons of the liposome platform in cancer targeting are discussed vis-à-vis nontargeted drugs, using as an example a liposome drug delivery system targeted to the folate receptor.
通过将聚乙二醇（PEG）衍生化脂质掺入脂质体双层来用PEG包覆脂质体，可抑制网状内皮系统对脂质体的摄取，并显著延长脂质体在血流中的停留时间。药物负载技术的同步发展提高了脂质体中药物包封的效率和稳定性，特别是对于阳离子两亲物如蒽环类药物而言。这种新一代脂质体的一个例子是聚乙二醇化脂质体阿霉素制剂，称为多柔比星脂质体（Doxil）或凯素（Caelyx），其临床药代动力学特征是血浆清除缓慢和分布容积小。这些长循环脂质体药物载体的一个标志是它们在肿瘤中的蓄积增强。这种被动靶向效应的潜在机制是被称为增强渗透与滞留（EPR）的现象，这已在多种实验性肿瘤类型中得到描述。除了被动靶向效应外，脂质体药物递送平台还提供了在脂质体膜上接枝肿瘤特异性配体以主动靶向肿瘤细胞并潜在地进行细胞内药物递送的可能性。以靶向叶酸受体的脂质体药物递送系统为例，相对于非靶向药物讨论了脂质体平台在癌症靶向中的优缺点。
