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免疫脂质体、F(ab')2和IgG在体内对红细胞的免疫特异性靶向作用。

Immunospecific targeting of immunoliposomes, F(ab')2 and IgG to red blood cells in vivo.

作者信息

Peeters P A, Oussoren C, Eling W M, Crommelin D J

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, State University of Utrecht, The Netherlands.

出版信息

Biochim Biophys Acta. 1988 Aug 18;943(2):137-47. doi: 10.1016/0005-2736(88)90545-7.

DOI:10.1016/0005-2736(88)90545-7
PMID:3401475
Abstract

In this report a model to study the fate of target cells in the blood circulation after injection of appropriate immunoliposomes is discussed. The effect of intravenous administration of antimouse RBC immunoliposomes, F(ab')2 or IgG on the fate of intravenously injected 51Cr-labelled mouse RBC (Cr-mRBC) in the mouse and, particularly, in the rat was studied. The immunoliposome was of the Fab'-MPBPE-REV type (Fab'-fragments covalently linked to reverse phase evaporation vesicles by maleimido-4-(p-phenylbutyrate)phosphatidylethanolamine). In the rat model a high blood level (80%) of the injected dose of target cells, Cr-mRBC, was maintained for several hours. The elimination by Fab'-liposomes, F(ab')2 or IgG of Cr-mRBC, and subsequent uptake into liver and spleen was dose dependent. Administration of Fab'-liposomes or F(ab')2 resulted in a preferential uptake into the spleen (above a certain dose also, but much lower, uptake into the liver was observed), while after IgG administration 51Cr-label was mainly recovered in the liver. At equal protein doses (+/- 130 micrograms) Fab'-liposomes induced a faster elimination of the Cr-mRBC and a higher uptake into the spleen than F(ab')2. The potential advantage of the use of drug-loaded immunoliposomes to eliminate target cells from the blood stream and to induce a certain pharmacological effect in the target cells, in comparison with the free antibody administration of F(ab')2 or IgG is discussed.

摘要

在本报告中,讨论了一种用于研究注射适当免疫脂质体后血液循环中靶细胞命运的模型。研究了静脉注射抗小鼠红细胞免疫脂质体、F(ab')2或IgG对小鼠(尤其是大鼠)静脉注射的51Cr标记小鼠红细胞(Cr-mRBC)命运的影响。免疫脂质体为Fab'-MPBPE-REV型(通过马来酰亚胺-4-(对苯基丁酸)磷脂酰乙醇胺将Fab'片段共价连接到反相蒸发囊泡)。在大鼠模型中,注射剂量的靶细胞Cr-mRBC在数小时内保持较高的血液水平(80%)。Fab'-脂质体、F(ab')2或IgG对Cr-mRBC的清除以及随后在肝脏和脾脏中的摄取呈剂量依赖性。Fab'-脂质体或F(ab')2的给药导致优先摄取到脾脏中(在一定剂量以上也观察到,但程度低得多,摄取到肝脏中),而在给予IgG后,51Cr标记主要在肝脏中回收。在相等的蛋白质剂量(±130微克)下,Fab'-脂质体比F(ab')2诱导更快地清除Cr-mRBC并更高地摄取到脾脏中。与游离抗体F(ab')2或IgG给药相比,使用载药免疫脂质体从血流中清除靶细胞并在靶细胞中诱导一定药理作用的潜在优势进行了讨论。

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