Polyester dendritic systems for drug delivery applications:: Design, synthesis, and characterization

被引:263
|
作者
Ihre, HR [1 ]
De Jesüs, OLP
Szoka, FC
Fréchet, JMJ
机构
[1] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA
[2] Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA
关键词
D O I
10.1021/bc010102u
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Attachment of drugs to high molecular weight polymers can significantly improve both tumor targeting and therapeutic efficacy due to the enhanced permeability and retention effect observed in tumor tissue. However, the commercial availability of well-defined water-soluble polymeric systems with narrow polydispersities that are biocompatible, nontoxic, and nonimmunogenic is rather limited. To address this need, we have investigated dendritic polymers as promising scaffolds for the preparation of new soluble polymeric drug carriers due to their well-defined molecular architecture and their multiplicity of surface sites. Herein we show the design and synthesis of dendritic polyester systems based on the monomer unit 2,2-bis(hydroxymethyl)propanoic acid as a possible versatile drug carrier. The potent anticancer drug doxorubicin was attached via a pH-sensitive linkage to one of the carriers presented, demonstrating the feasibility of using these polyester dendritic structures to prepare a viable polymer-drug conjugate.
引用
收藏
页码:443 / 452
页数:10
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