Kojima C, Kono K, Maruyama K, Takagishi T
Department of Applied Materials Science, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Sakai, Osaka 599-8531, Japan.
Bioconjug Chem. 2000 Nov-Dec;11(6):910-7. doi: 10.1021/bc0000583.
Polyamidoamine dendrimers having poly(ethylene glycol) grafts were designed as a novel drug carrier which possesses an interior for the encapsulation of drugs and a biocompatible surface. Poly(ethylene glycol) monomethyl ether with the average molecular weight of 550 or 2000 was combined to essentially every chain end of the dendrimer of the third or fourth generation via urethane bond. The poly(ethylene glycol)-attached dendrimers encapsulating anticancer drugs, adriamycin and methotrexate, were prepared by extraction with chloroform from mixtures of the poly(ethylene glycol)-attached dendrimers and varying amounts of the drugs. Their ability to encapsulate these drugs increased with increasing dendrimer generation and chain length of poly(ethylene glycol) grafts. Among the poly(ethylene glycol)-attached dendrimers prepared, the highest ability was achieved by the dendrimer of the fourth generation having the poly(ethylene glycol) grafts with the average molecular weight of 2000, which could retain 6.5 adriamycin molecules or 26 methotrexate molecules/dendrimer molecule. The methotrexate-loaded poly(ethylene glycol)-attached dendrimers released the drug slowly in an aqueous solution of low ionic strength. However, in isotonic solutions, methotrexate and adriamycin were readily released from the poly(ethylene glycol)-attached dendrimers.
带有聚乙二醇接枝的聚酰胺-胺树枝状大分子被设计为一种新型药物载体，它具有用于封装药物的内部空间和生物相容性表面。平均分子量为550或2000的聚乙二醇单甲醚通过脲烷键连接到第三代或第四代树枝状大分子的基本上每个链端。通过用氯仿从聚乙二醇接枝树枝状大分子与不同量药物的混合物中萃取，制备了封装抗癌药物阿霉素和甲氨蝶呤的聚乙二醇连接树枝状大分子。它们封装这些药物的能力随着树枝状大分子代数的增加和聚乙二醇接枝链长度的增加而提高。在所制备的聚乙二醇连接树枝状大分子中，具有平均分子量为2000的聚乙二醇接枝的第四代树枝状大分子实现了最高的封装能力，其每个树枝状大分子分子可保留6.5个阿霉素分子或26个甲氨蝶呤分子。负载甲氨蝶呤的聚乙二醇连接树枝状大分子在低离子强度的水溶液中缓慢释放药物。然而，在等渗溶液中，甲氨蝶呤和阿霉素很容易从聚乙二醇连接树枝状大分子中释放出来。
