ERYTHROCYTES AS CARRIERS OF CHEMOTHERAPEUTIC-AGENTS FOR TARGETING THE RETICULOENDOTHELIAL SYSTEM
ERYTHROCYTES AS CARRIERS OF CHEMOTHERAPEUTIC-AGENTS FOR TARGETING THE RETICULOENDOTHELIAL SYSTEM
复制标题
DOI：
10.1002/ajh.2830090303
复制
发表时间：
1980-01-01
影响因子：
12.8
通讯作者：
GHAFFAR, A
中科院分区：
文献类型：
--
作者：
LYNCH, WE;SARTIANO, GP;GHAFFAR, A
这项工作的目的是确定一种模型，该模型使用低渗装载的红细胞作为载体，将药物靶向RES。C.细胞的总体积。在这些条件下，1/3可以用低渗药物溶液代替。胞嘧啶-β- D-阿拉伯呋喃糖苷（araC）具有膜渗透性，不能包埋在红细胞中，磷酸化使其能够被有效地负载。放线菌素D可以在0 ℃下装载并保留在细胞内。但在37 ℃下1分钟内90%的这种负载的药物从红细胞中漏出。C.放线菌素D-DNA复合物，可以加载和保留更长的时间。在这种情况下，50%的DNA结合药物在37 ℃下保留在细胞中1小时。C.糖肽类抗肿瘤抗生素博来霉素可包埋并保留在细胞中而无明显渗漏。在Balb/C和C_3H小鼠中，包埋在红细胞中的博莱霉素比相同剂量的游离药物对RES吞噬功能的抑制作用显著增强。讨论了可能使用这些药物，包埋在红细胞中，用于生产的RES封锁在治疗疾病的人的理由。
The object of this work was to define a model using hypotonically loaded erythrocytes as a vehicle to target drugs to the RES. The optimum hemolytic event occurs at 100 mOsm[milliosmoles]/kg using a 0.5-min exposure at 0.degree. C. Of the total volume of the cells .apprx. 1/3 could be replaced with hypotonic drug solutions under these conditions. Cytosine-.beta.-D-arabinofuranoside, ara C, is membrane permeable and could not be entrapped in the erythrocytes, phosphorylation of this nucleoside antimetabolite enabled it to be loaded efficiently. Actinomycin D could be loaded and retained within the cells at 0.degree. C, but 90% of this loaded drug leaked out of the erythrocytes in 1 min at 37.degree. C. Actinomycin D-DNA complexes, could be loaded and retained for longer periods. In this case, 50% of the DNA-bound drug was retained in the cells for 1 h at 37.degree. C. The glycopeptide antitumor antibiotic, bleomycin, could be entrapped and retained in the cells without appreciable leakage. It was possible to load a human therapeutic dose of this drug in 1-2 ml of packed cells, Bleomycin entrapped in erythrocytes was significantly more effective than the same dose of free drug in suppressing the phagocytic function of the RES in Balb/C and C3H mice. The rationale is discussed for the possible use of these drugs, entrapped in erythrocytes, for the production of RES blockade in the treatment of disorders in man.