Synthesis of Polyamidoamine Dendrimers Having Poly(ethylene glycol) Grafts and Their Ability To Encapsulate Anticancer Drugs

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• 作者：Chie Kojima ; Kenji Kono ; Kazuo Maruyama ; and Toru Takagishi
• 刊名：Bioconjugate Chemistry
• 出版年：2000
• 出版时间：November 2000
• 年：2000
• 卷：11
• 期：6
• 页码：910 - 917
• 全文大小：107K
• 年卷期：v.11,no.6(November 2000)
• ISSN：1520-4812

文摘

Polyamidoamine dendrimers having poly(ethylene glycol) grafts were designed as a novel drug carrierwhich possesses an interior for the encapsulation of drugs and a biocompatible surface. Poly(ethyleneglycol) monomethyl ether with the average molecular weight of 550 or 2000 was combined to essentiallyevery 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)-attacheddendrimers and varying amounts of the drugs. Their ability to encapsulate these drugs increasedwith increasing dendrimer generation and chain length of poly(ethylene glycol) grafts. Among thepoly(ethylene glycol)-attached dendrimers prepared, the highest ability was achieved by the dendrimerof the fourth generation having the poly(ethylene glycol) grafts with the average molecular weight of2000, 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 anaqueous solution of low ionic strength. However, in isotonic solutions, methotrexate and adriamycinwere readily released from the poly(ethylene glycol)-attached dendrimers.