Bioconjugate Chem. 2002, 13, 443−452
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Polyester Dendritic Systems for Drug Delivery Applications: Design, Synthesis, and Characterization Henrik R. Ihre,† Omayra L. Padilla De Jesu´s,† Francis C. Szoka, Jr.,*,‡ and Jean M. J. Fre´chet*,† Department of Chemistry, University of California, Berkeley, California 94720-1460 and School of Pharmacy, University of California, San Francisco, California 94143-0446. Received October 22, 2001
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.
INTRODUCTION
In the past few decades, there has been an increasing interest in the design and synthesis of polymeric systems with potential drug delivery applications, a concept initially introduced by Ringsdorf (1, 2) and Kopecˇek (35). For certain medical treatments, such as chemotherapy, the use of high molecular weight (>20 000 Da) systems provide advantages compared to low molecular weight molecules (
