The role of the size and number of polyethylene glycol chains in the biodistribution and tumor localization of triazine dendrimers

Mol Pharm. 2008 Jul-Aug;5(4):540-7. doi: 10.1021/mp8000292.

Abstract

The synthesis and biodistribution of three triazine dendrimers differing in PEGylation are described. Dendrimers 1, 2, and 3 are derived from a common intermediate, dendrimer 4, and vary in molecular mass from 11 to 73 kDa as a result of PEGylation with multiple (theoretically, 16) PEG groups of 0.6, 2, and 5 kDa, respectively. As expected, elimination half-lives increased with an increase in molecular mass. In light of other results, however, molecular mass proves not to be the primary determinant of elimination half-lives. Instead, these times can be more readily predicted from the number of PEG groups on the dendrimer: the size of the PEG chain contributes to a lesser extent. Tumor uptake is observed for all the three dendrimers in mice bearing prostate cancer xenografts.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Dendrimers / chemical synthesis
  • Dendrimers / chemistry*
  • Dendrimers / metabolism
  • Dendrimers / pharmacokinetics*
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Structure
  • Molecular Weight
  • Neoplasms / pathology*
  • Polyethylene Glycols / chemistry*
  • Spleen / drug effects
  • Spleen / metabolism
  • Tissue Distribution
  • Triazines / chemistry*
  • Xenograft Model Antitumor Assays

Substances

  • Dendrimers
  • Triazines
  • Polyethylene Glycols