Biological evaluation of polyester dendrimer: Poly(ethylene oxide) "bow-tie" hybrids with tunable molecular weight and architecture

Elizabeth R. Gillies, Edward Dy, Jean Frechet*, Francis C. Szoka

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

227 Citations (SciVal)

Abstract

High molecular weight (MW) polymers have shown promise in terms of improving the properties and the efficacy of low MW therapeutics. However, new systems that are highly biocompatible, are biodegradable, have well-defined MW, and have multiple functional groups for drug attachment are still needed. The biological evaluation of a library of eight polyester dendrimer-poly(ethylene oxide) (PEO) bow-tie hybrids is described here. The group of evaluated polymers was designed to include a range of MWs (from 20000 to 160000) and architectures with the number of PEO arms ranging from two to eight. In vitro experiments revealed that the polymers were nontoxic to cells and were degraded to lower MW species at pH 7.4 and pH 5.0. Biodistribution studies with 125|- radiolabeled polymers showed that the high MW carriers (>40000) exhibited long circulation half-lives. Comparison of the renal clearances for the four-arm versus eight-arm polymers indicated that the more branched polymers were excreted more slowly into the urine, a result attributed to their decreased flexibility. Due to their essentially linear architecture that does not provide for good isolation of the iodinated phenolic moieties, the polymers with "two arms" were rapidly taken up by the liver. The biodistributions of two long-circulating high MW polymers in mice bearing subcutaneous B16F10 tumors were evaluated, and high levels of tumor accumulation were observed. These new carriers are therefore promising for applications in drug delivery and are also useful for improving our understanding of the effect of polymer architecture on pharmacokinetic properties.

Original languageEnglish (US)
Pages (from-to)129-138
Number of pages10
JournalMolecular Pharmaceutics
Volume2
Issue number2
DOIs
StatePublished - Mar 1 2005

Keywords

  • Biodegradable
  • Biodistribution
  • Dendrimer
  • Drug delivery
  • Polymer
  • Tumor

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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