Design, Synthesis, and Biological Evaluation of a Robust, Biodegradable Dendrimer

作者：van der Poll Derek G; Kieler Ferguson Heidi M; Floyd William C; Guillaudeu Steven J; Jerger Katherine; Szoka Francis C^*; Frechet Jean M

来源：Bioconjugate Chemistry, 2010, 21(4): 764-773.

DOI：10.1021/bc900553n

PEGylated dendrimers are attractive for biological applications due to their tunable pharmacokinetics and ability to carry multiple copies of bioactive molecules. The rapid and efficient synthesis of a robust and biodegradable PEGylated dendrimer based on a polyester polyamide hybrid core is described. The architecture is designed to avoid destructive side reactions during dendrimer preparation while maintaining biodegradability. Therefore, a dendrimer functionalized with doxorubicin (Dox) was prepared from commercial starting materials in nine, high-yielding linear steps. Both the dendrimer and Doxil were evaluated in parallel using equimolar dosage in the treatment of C26 murine colon carcinoma, leading to statistically equivalent results with most mice tumor-free at the end of the 60 day experiment. The attractive features of this dendritic drug carrier are its simple synthesis, biodegradability, and versatility for application to a variety of drug payloads with high drug loadings.

• 出版日期2010-4