Maruyama K
Department of Pharmaceutics, Teikyo University.
Nihon Rinsho. 1998 Mar;56(3):632-7.
The current status of newly developed polyethyleneglycol coated liposome (PEG-liposome) were described in this review. Liposomes have demonstrated considerable promise as a carrier for the delivery of drugs in vivo. However, one of the drawback is that most liposomes intravenously injected into animals are rapidly removed from the blood circulation by uptake primarily in the cells of reticuloendothelial system (RES). It has been found that PEG-liposome are not readily taken up by the macrophages in the RES and hence stay in the circulation for a relatively long period of time. Pharmacokinetic analysis and therapeutic studies with tumor bearing mice revealed that PEG-liposomes have considerable potential as drug carriers for cancer therapy. Elevated liposome accumulation has been found in the tumor bearing mice model system. Results from clinical studies with doxorubicin encapsulated into PEG-liposomes (DOXIL) in AIDS-related Kaposi's sarcoma revealed an increased therapeutic efficacy compared to free-drug. These new formulations of long-circulating liposomes (PEG-liposome) offer the development of immunoliposomes with both long survival times in circulation and target recognition being retained in vivo. Fab'-PEG-immunoliposome was newly designed to gain long-circulating enough to extravasate to the targeted solid tumor in vivo. An ultimate goal of Fab'-PEG-immunoliposome is the incorporation of a fusogenic molecules that would induce fusion of liposome following their binding to the target cells or their internalization by endocytosis. Such liposomal formulations should be useful for endocytotic internalization of plasmid DNA and other bioactive materials.
本综述描述了新开发的聚乙二醇包被脂质体（PEG脂质体）的当前状况。脂质体作为体内药物递送载体已显示出相当大的前景。然而，缺点之一是大多数静脉注射到动物体内的脂质体主要通过网状内皮系统（RES）细胞摄取而迅速从血液循环中清除。已发现PEG脂质体不易被RES中的巨噬细胞摄取，因此在循环中停留相对较长时间。对荷瘤小鼠的药代动力学分析和治疗研究表明，PEG脂质体作为癌症治疗的药物载体具有相当大的潜力。在荷瘤小鼠模型系统中发现脂质体积累增加。对艾滋病相关卡波西肉瘤中封装在PEG脂质体（DOXIL）中的阿霉素进行临床研究的结果显示，与游离药物相比，治疗效果有所提高。这些新的长循环脂质体（PEG脂质体）制剂为开发在循环中具有长存活时间且在体内保留靶标识别能力的免疫脂质体提供了可能。Fab'-PEG免疫脂质体是新设计的，以获得足够长的循环时间以便在体内渗出到靶向实体瘤中。Fab'-PEG免疫脂质体的最终目标是掺入一种融合分子，该分子在与靶细胞结合或通过内吞作用内化后会诱导脂质体融合。这种脂质体制剂应有助于质粒DNA和其他生物活性物质的内吞内化。
