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体外人工合成的1,3 - 二酰胺磷脂对脂质体诱导的补体激活作用的惊人缺失。

Surprising lack of liposome-induced complement activation by artificial 1,3-diamidophospholipids in vitro.

作者信息

Bugna Simon, Buscema Marzia, Matviykiv Sofiya, Urbanics Rudolf, Weinberger Andreas, Meszaros Tamas, Szebeni Janos, Zumbuehl Andreas, Saxer Till, Müller Bert

机构信息

Biomaterials Science Center, University of Basel, Allschwil, Switzerland.

Nanomedicine Research and Education Center, Semmelweis University, Budapest, Hungary.

出版信息

Nanomedicine. 2016 Apr;12(3):845-849. doi: 10.1016/j.nano.2015.12.364. Epub 2015 Dec 28.

Abstract

UNLABELLED

Cardio-vascular diseases are the main cause of death, emphasizing the need to improve patient treatment and survival. One therapeutic approach is a liposome-based drug carrier system specifically targeting constricted arteries. The recently discovered mechano-sensitive liposomes use hemodynamic shear-stress differences between healthy and constricted blood vessels as trigger for drug release. Liposomes are promising delivery containers but are being recognized as foreign by the immune system. Complement activation as essential factor of the recognition leads to adverse effects. Here, we tested complement activation by liposomes formulated from the artificial phospholipid Pad-PC-Pad in vitro. Surprisingly no complement activation was detected in human sera and porcine plasma. In in vivo experiments with three pigs, neither anaphylactic reactions nor other significant hemodynamic changes were observed even at comparably high liposome doses. The pilot study holds promise for an absence of complement-mediated adverse effects of Pad-PC-Pad liposomes in human.

FROM THE CLINICAL EDITOR

A lot of research has been done on new treatment for cardiovascular diseases. Liposome-based carrier systems have also shown promises. In this article, the authors studied the potential risks of complement activation by liposomes in in-vivo experiments. The absence of complement activation by Pad-PC-Pad liposomes may indicate its use in humans.

摘要

未标注

心血管疾病是主要死因,这凸显了改善患者治疗和提高生存率的必要性。一种治疗方法是基于脂质体的药物载体系统,专门针对狭窄动脉。最近发现的机械敏感脂质体利用健康血管和狭窄血管之间的血流动力学剪切应力差异作为药物释放的触发因素。脂质体是很有前景的给药载体,但被免疫系统识别为外来物。补体激活作为识别的关键因素会导致不良反应。在此,我们在体外测试了由人工磷脂Pad-PC-Pad制备的脂质体的补体激活情况。令人惊讶的是,在人血清和猪血浆中未检测到补体激活。在对三头猪进行的体内实验中,即使使用相当高剂量的脂质体,也未观察到过敏反应或其他显著的血流动力学变化。这项初步研究表明Pad-PC-Pad脂质体在人体中不存在补体介导的不良反应。

临床编辑评论

针对心血管疾病的新治疗方法已经开展了大量研究。基于脂质体的载体系统也显示出前景。在本文中,作者在体内实验中研究了脂质体补体激活的潜在风险。Pad-PC-Pad脂质体未激活补体可能表明其可用于人体。

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