Gabizon A, Goren D, Cohen R, Barenholz Y
Sharet Institute of Oncology, Hadassah Hebrew University, Medical Center, Jerusalem, Israel.
J Control Release. 1998 Apr 30;53(1-3):275-9. doi: 10.1016/s0168-3659(97)00261-7.
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.
脂质体载体的血浆清除率以及脂质体 - 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以及各个组织的血管通透性将决定其外渗和生物分布情况。与游离阿霉素相比，聚乙二醇（PEG）脂质体阿霉素的药代动力学特征是循环半衰期极长、血浆清除缓慢且分布容积减小。与游离形式的阿霉素相比，这些载体系统显示出改善的外渗情况，在肿瘤中的定位增强且治疗效果更佳。这些特性是优化脂质体组成以及采用特殊载药方法的结果，该方法可产生稳定且循环时间长的载体。在临床研究中，包裹在PEG包被脂质体中的阿霉素显示出独特的药代动力学 - 毒性特征以及有前景的抗肿瘤活性。
