Development of liposomal anthracyclines: from basics to clinical applications
Development of liposomal anthracyclines: from basics to clinical applications
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DOI：
10.1016/s0168-3659(97)00261-7
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发表时间：
1998-04-30
影响因子：
10.8
通讯作者：
Barenholz, Y
中科院分区：
文献类型：
--
作者：
Gabizon, A;Goren, D;Barenholz, Y
脂质体包膜药物的药代动力学受两个变量的相互作用控制：脂质体载体的血浆清除率和脂质体-药物在血流中的结合稳定性。脂质体药物的药代动力学特性、脂质体载体的囊泡大小和单个组织的血管通透性将决定外渗和生物分布概况。聚乙二醇-(PEG)-脂质体阿霉素的药代动力学特点是与游离阿霉素相比，循环半衰期极长，血浆清除率慢，分布体积小。与自由形式的阿霉素相比，这些载体系统表现出更好的外渗特征，增强了肿瘤的定位和优越的治疗效果。这些特性是优化的脂质体组成和一种特殊的载药方法的结果，这种方法产生稳定和长循环的载体。在临床研究中，包裹在聚乙二醇包被脂质体中的阿霉素显示出独特的药代动力学毒性特征和有希望的抗肿瘤活性。(C) 1998爱思唯尔科学有限公司
The pharmacokinetics of liposome-encapsulated drugs are controlled by the interplay of two variables: the rate of plasma clearance of the liposome carrier, and the stability of the liposome-drug association in the blood stream. The pharmacokinetic properties of the liposomal drug, the vesicle size of the liposome carrier and the vascular permeability of individual tissues will determine the extravasation and biodistribution profile. The pharmacokinetics of polyethylene-glycol-(PEG)-liposomal doxorubicin are characterized by an extremely long circulating half-life, slow plasma clearance and reduced volume of distribution compared to free doxorubicin. These carrier systems show an improved extravasation profile with enhanced localization in tumors and superior therapeutic efficacy in comparison to doxorubicin in free form. These properties are the result of an optimized liposome composition and of a special drug-loading method which produces stable and long-circulating carriers. In clinical studies, doxorubicin encapsulated in PEG-coated liposomes shows a unique pharmacokinetic-toxicity profile and promising antitumor activity. (C) 1998 Elsevier Science B.V.