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

doi:10.1002/app.29047

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 journal › Article › peer-review

19 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	444-451
Number of pages	8
Journal	Journal of Applied Polymer Science
Volume	111
Issue number	1
DOIs	https://doi.org/10.1002/app.29047
State	Published - Jan 5 2009
Externally published	Yes

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/app.29047

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abstract = "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.",

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T1 - Water-soluble poly(ethylene glycol) prodrug of pemetrexed

T2 - synthesis, characterization, and preliminary cytotoxicity

AU - Min, Tao

AU - Ye, Hai

AU - Zhang, Peng

AU - Liu, Jun

AU - Zhang, Can

AU - Shen, Wenbin

AU - Wang, Wan

AU - Shen, Longsheng

PY - 2009/1/5

Y1 - 2009/1/5

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AB - 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.

KW - Conjugated polymers

KW - Drug delivery systems

KW - Hydrophilic polymers

KW - Synthesis

KW - Water-soluble polymers

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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