Todd J A, Levine A M, Tökés Z A
J Natl Cancer Inst. 1980 Apr;64(4):715-9.
The uptake of free and liposome-entrapped methotrexate (MTX) by human chronic lymphocytic leukemia cells was compared under incubation conditions resembling those encountered in vivo. Liposome encapsulation enhanced up to 200 times the association of MTX with these cells. Autoradiographic studies established an association of [3H]MTX liposomes with the cells. Such a mode of delivery did not significantly increase the amount of drug available to inhibit dihydrotolate dehydrogenase, which suggested that the liposome content was not readily available to the cytoplasmic sites of action. Increased doses of encapsulated MTX resulted in enzyme inhibitions that were similar to those obtained with the free drug. This finding demonstrates that higher doses of MTX delivered by liposomes could be potentially useful in overcoming drug-transport resistance.
在类似于体内情况的孵育条件下，比较了人慢性淋巴细胞白血病细胞对游离甲氨蝶呤（MTX）和脂质体包裹的甲氨蝶呤的摄取。脂质体包封使MTX与这些细胞的结合增强了200倍。放射自显影研究证实了[3H]MTX脂质体与细胞的结合。这种给药方式并没有显著增加可用于抑制二氢叶酸还原酶的药物量，这表明脂质体中的药物不易到达细胞质作用部位。增加包裹MTX的剂量会导致酶抑制作用，这与游离药物所产生的抑制作用相似。这一发现表明，通过脂质体递送更高剂量的MTX可能有助于克服药物转运抗性。
