Zimmermann U, Pilwat G
Z Naturforsch C Biosci. 1976 Nov-Dec;31(11-12):732-6.
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 or gan 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.
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空给药。用于癌症治疗的甲氨蝶呤药物的载药细胞有效性得到了证明。使用介电击穿技术将甲氨蝶呤载入红细胞。介电击穿导致细胞膜通透性短暂增加。将载有氚标记甲氨蝶呤的红细胞注入小鼠体内，并测量几个器官中的活性水平随时间的变化。结果表明，使用这种药物递送系统，超过50%的药物（10分钟后）可在肝脏中积累，并且该器官中的高活性水平可维持3小时以上。另一方面，以常规方式注射溶液给药，甲氨蝶呤在肝脏中的积累量仅为25%（10分钟后）。1至2小时后药物完全排出。建议同时将红细胞与顺磁性或铁磁性物质载入，以获得针对身体任何选定部位的器官特异性。
