Yokoyama M, Miyauchi M, Yamada N, Okano T, Sakurai Y, Kataoka K, Inoue S
Institute of Biomedical Engineering, Tokyo Women's Medical College, Japan.
Cancer Res. 1990 Mar 15;50(6):1693-700.
Adriamycin (ADR), an anthracycline anticancer drug, was bound to the poly(aspartic acid) chain of poly(ethylene glycol)-poly(aspartic acid) block copolymer by amide bond formation between an amino group of Adriamycin and the carboxyl groups of the poly(aspartic acid) chain. The polymeric drug thus obtained was observed to form a micelle structure possessing diameter of approximately 50 nm, with a narrow distribution, in phosphate-buffered saline and to show excellent water solubility despite a large amount of ADR introduction. Further, it was able to be stored in lyophilized form without losing its water solubility in the redissolving procedure. Increased stability of the bound Adriamycin molecules in phosphate-buffered saline and elimination of binding affinity for bovine serum albumin due to the micelle formation were further advantages of this polymeric drug. In vivo high anticancer activity of this micelle-forming polymeric drug against P 388 mouse leukemia was obtained with less body weight loss than that seen with free ADR, due to low toxicity as compared with free ADR.
阿霉素（ADR）是一种蒽环类抗癌药物，通过阿霉素的氨基与聚天冬氨酸链的羧基之间形成酰胺键，将其与聚乙二醇-聚天冬氨酸嵌段共聚物的聚天冬氨酸链结合。观察到由此获得的聚合物药物在磷酸盐缓冲盐水中形成直径约为50nm的胶束结构，分布狭窄，并且尽管引入了大量的阿霉素，仍表现出优异的水溶性。此外，它能够以冻干形式储存，在重新溶解过程中不会失去其水溶性。结合的阿霉素分子在磷酸盐缓冲盐水中稳定性增加以及由于胶束形成而消除了对牛血清白蛋白的结合亲和力是这种聚合物药物的进一步优点。与游离阿霉素相比，由于毒性较低，这种形成胶束的聚合物药物对P 388小鼠白血病具有体内高抗癌活性，且体重减轻比游离阿霉素少。
