PEG prodrug of gambogic acid: Amino acid and dipeptide spacer effects

Ya Ding, Peng Zhang, Xiao Yan Tang, Can Zhang*, Song Ding, Hai Ye, Qi Long Ding, Wen Bin Shen, Qi Neng Ping

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The clinical application of gambogic acid (GA), a natural component with promising antitumor activity, was limited due to its extremely poor aqueous solubility, rapid elimination in vivo, and wide biodistribution. To solve these problems, 30 poly(ethylene glycol)-amino acid (or dipeptide)-gambogic acid (PEG-spacer-GA) conjugates were synthesized. All polymeric prodrugs showed satisfactory aqueous solubility (1.2 × 103-4.5 × 10 5 times of GA solubility). It was found that the molecular weight of PEG and the choice of spacers played important role in controlling the drug percentage, water solubility, and drug release properties of PEG-GA conjugates with and without spacers. Studies of pharmacokinetics, biodistribution, and cell cytotoxicity revealed that, employing the polymeric conjugation strategy, the remarkably improved circulatory retention time and bioavailability, as well as reduced peripheral toxicity were obtained in comprising with GA and its Cremophor EL formulation. The liver target character of PEG-GA conjugates made them potential prodrugs for liver cancer treatment.

Original languageEnglish (US)
Pages (from-to)1694-1702
Number of pages9
JournalPolymer
Volume53
Issue number8
DOIs
StatePublished - Apr 3 2012
Externally publishedYes

Keywords

  • Gambogic acid
  • Poly(ethylene glycol)
  • Polymeric prodrug

ASJC Scopus subject areas

  • Organic Chemistry
  • Polymers and Plastics
  • Materials Chemistry

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