Water-soluble poly(ethylene glycol) prodrug of pemetrexed: synthesis, characterization, and preliminary cytotoxicity

Tao Min, Hai Ye, Peng Zhang, Jun Liu, Can Zhang*, Wenbin Shen, Wan Wang, Longsheng Shen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Pemetrexed is a. novel antifolate of antimetabolite with multiple enzyme targets involved in both pyrimidine and purine synthesis. It has entered the clinical usage due to favorable profiles especially in the cancer treatment of mesothelioma and non-small-cell lung carcinoma. But it presents numerous challenges associated with poor water solubility and unstabillty in its original form of glutamic acid. The aim of this study is to solubilize pemetrexed by designing and synthesizing its aqueous-soluble prodrug using high aqueous-soluble polymeric carrier poly(ethylene glycol) (PEG). A new type of soluble pemetrexed prodrug was synthesized with dihydroxyl PEG and a single amino acid linkage, and was extensively characterized using 1H-NMR, 13C-NMR, Fourier-transform infrared, and matrix-assisted laser desorption time of flight mass spectrometry. In addition, the prodrugs were evaluated for the drug loading capability, the aqueous solubility, and the preliminary in vitro cytotoxicity. The results indicate that the new PEGylated pemetrexed conjugates possess enhanced water solubility and stability, and provide another feasible choice of the pharmaceutical form of pemetrexed in the clinical application.

Original languageEnglish (US)
Pages (from-to)444-451
Number of pages8
JournalJournal of Applied Polymer Science
Issue number1
StatePublished - Jan 5 2009
Externally publishedYes


  • Conjugated polymers
  • Drug delivery systems
  • Hydrophilic polymers
  • Synthesis
  • Water-soluble polymers

ASJC Scopus subject areas

  • Chemistry(all)
  • Surfaces, Coatings and Films
  • Polymers and Plastics
  • Materials Chemistry


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