In vitro and in vivo comparison of immunoliposomes made by conventional coupling techniques with those made by a new post-insertion approach

被引:191
作者
Iden, DL [1 ]
Allen, TM [1 ]
机构
[1] Univ Alberta, Dept Pharmacol, Edmonton, AB T6G 2H7, Canada
来源
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES | 2001年 / 1513卷 / 02期
基金
加拿大健康研究院;
关键词
immunoliposome; anti-CD19; B-cell lymphoma; doxorubicin; targeted drug delivery system; ligand-mediated targeting; polyethylene glycol;
D O I
10.1016/S0005-2736(01)00357-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ligand-targeted liposomes have the potential to increase the therapeutic efficacy of antineoplastic agents. Recently, a combinatorial approach to the preparation of ligand-targeted liposomes has been developed, termed the post-insertion technique, which will facilitate the production of targeted liposomes. In this paper, Stealth immunoliposomes (SIL) coupled to anti-CD19 made by either a conventional coupling technique (SIL[anti-CD19]), or by the post-insertion technique (PIL[anti-CD19], were compared with respect to their in vitro binding and cytotoxicity and their ability to improve in vivo survival in tumor-bearing mice, The in vitro binding and uptake of PIL[anti-CD19] by CD19-expressing, B-cell lymphoma (Namalwa) cells was similar to that of SIL[anti-CD19] and both were significantly higher than binding of non-targeted liposomes (SL). In addition, no significant differences were found between the respective in vitro cytotoxicities of doxorubicin-loaded PIL[anti-CD19] or SIL[anti-CD19]. or in their in vivo therapeutic efficacy in a murine model of human B-lymphoma. Overall, the results demonstrate that the post-insertion technique is a simple, flexible and effective means for preparing targeted liposomal drugs for clinical applications. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:207 / 216
页数:10
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