Pros and cons of the liposome platform in cancer drug targeting
Pros and cons of the liposome platform in cancer drug targeting
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DOI：
10.1080/08982100600848769
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发表时间：
2006-01-01
影响因子：
4.4
通讯作者：
Zalipsky, Samuel
中科院分区：
文献类型：
--
作者：
Gabizon, Alberto A.;Shmeeda, Hilary;Zalipsky, Samuel
通过在PEG衍生脂质的脂质体双层中掺入聚乙二醇（PEG）来涂覆脂质体导致网状内皮系统对脂质体摄取的抑制和脂质体在血流中的停留时间的显著延长。载药技术的平行发展提高了脂质体中药物包封的效率和稳定性，特别是关于阳离子两亲物如蒽环类药物。这种新一代脂质体的一个例子是称为Doxil（R）或Caelyx（R）的聚乙二醇化脂质体多柔比星的制剂，其临床药代动力学特征在于缓慢的血浆清除和小的分布体积。这些长循环脂质体药物载体的标志是它们在肿瘤中的增强的积累。这种被动靶向效应的机制是被称为增强的渗透性和保留（EPR）的现象，它已在多种实验肿瘤类型中描述。除了被动靶向作用之外，脂质体药物递送平台还提供了将肿瘤特异性配体移植到脂质体膜上以主动靶向肿瘤细胞和潜在的细胞内药物递送的可能性。脂质体平台在癌症靶向中的优点和缺点被讨论相对于非靶向药物，作为一个例子，使用靶向叶酸受体的脂质体药物递送系统。
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 (R) or Caelyx (R), 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-a-vis nontargeted drugs, using as an example a liposome drug delivery system targeted to the folate receptor.