[Organ specific application of drugs by means of cellular capsule systems (author's transl)].
[Organ specific application of drugs by means of cellular capsule systems (author's transl)].
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DOI：
10.1007/978-3-642-51881-2_97
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发表时间：
1976
期刊：
影响因子：
--
通讯作者：
U. Zimmermann;G. Pilwat
中科院分区：
文献类型：
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作者：
U. Zimmermann;G. Pilwat
建议使用活细胞（红细胞、淋巴细胞和白细胞）作为药物递送系统，用于人类治疗和诊断中的时间和空间给药。载药细胞的有效性被证明是用于治疗癌症的药物甲氨蝶呤。使用介电击穿技术将甲氨蝶呤负载在红细胞上。介电击穿导致细胞膜渗透性的瞬时增加。将载有氚标记的甲氨蝶呤的红细胞注射到小鼠体内，并在几个器官中测量活性水平作为时间的函数。结果表明，使用该药物递送系统，超过50%的药物（10分钟后）可以在肝脏中积累，并且高活性水平可以在该器官中持续超过3小时。另一方面，以常规方式注射该药物仅导致25%的甲氨蝶呤在肝脏中蓄积（10分钟后）。药物在1至2小时后完全排出体外。建议将红细胞同时装载对位或铁磁性物质，以获得对身体任何选定部位的器官特异性。淋巴细胞也可用于将药物导向生物体的选定部位，因此淋巴细胞载体系统对克服脑-血液屏障和靶向药物的大脑。它表明，淋巴细胞可以加载电没有细胞膜的完整性和细胞功能的损失。
It is suggested to use living cells (red blood cells, lymphocytes and leucocytes) as drug delivery systems for temporal and spatial drug administration in human therapeutics and diagnosis. The effectiveness of drug loaded cells is demonstrated for the drug methotrexate which is used in cancer treatment.Red blood cells are loaded with methotrexate using the dielectric breakdown technique. Dielectric breakdown leads to a transient increase of permeability of the cell membrane. Red blood cells loaded with tritium-labelled methotrexate were injected into mice and the activity level was measured in several organs as a function of time. It is shown that with this drug delivery system more than 50% of the drug (after 10 min) can be accumulated in the liver and that a high activity level can be sustained in this organ for more than 3 hours. On the other hand, administration of this drug by injecting solutions in the usual manner leads only to an 25% accumulation of methotrexate (after 10 min) in the liver. The drug is excreted completely after 1 to 2 hours.It is proposed to load red blood cells simultaneously with para-or ferromagnetic substances to obtain organ-specificity for any selected site of the body.Lymphocytes can also be used for directing drugs to selected sites of the organism whereby the lymphocyte cárrier system is of considerable interest to overcome the brain-blood barrier and to target drugs to the brain.It is demonstrated that lymphocytes can be loaded electrically without loss of cell membrane integrity and cellular functions.