Synthesis and characterization of methotrexate polyethylene glycol esters as a drug delivery system

Chemical & Pharmaceutical Bulletin
Gholamhossein YousefiAlireza Shafaati

Abstract

Methotrexate (MTX) is one of the most common anticancer drugs used for chemotherapy so far. However some problems such as high toxicity and short plasma half-life, have limited its use. To overcome these limitations, conjugation with polymers such as polyethylene glycol (PEG) is one the efficient approaches which has been attempted in recent years. The aim of the present study is to synthesize esters of MTX with PEGs of different molecular weights and to characterize their physicochemical properties. Polymeric esters (MTX-PEGs) of MTX with low, medium and high molecular weight PEGs (750 D, 5000 D and 35000 D, respectively) were synthesized using dicyclohexylcarbodiimide (DCC) as coupling agent and triethylamine (TEA) as catalyst. The purification was carried out using preparative TLC. Purified esters were characterized by UV, IR and (1)H-NMR spectroscopy methods and their thermal behavior was studied by differential scanning calorimetry (DSC). Also, an isocratic HPLC method with three mobile phase systems was set to determine the partition coefficient of the esters (log P). Gel permeation chromatography (GPC) was utilized for molecular weight determination of esters, which proved 1 : 1 conjugation of drug with each polymer. The...Continue Reading

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Citations

Jun 7, 2013·Drug Delivery·Adriana De Fátima PereiraGisele Rodrigues Da Silva
Jul 12, 2012·Drug Development and Industrial Pharmacy· AjazuddinParijat Kanaujia
Nov 16, 2010·Photochemistry and Photobiology·Sergii RudiukIsabelle Rico-Lattes
Jul 10, 2012·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Azade TaheriSeyed Nasser Ostad
May 8, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Kaushik ThankiSanyog Jain
Jan 8, 2013·Cancer Chemotherapy and Pharmacology·Samira Sadat AbolmaaliRassoul Dinarvand
Mar 27, 2017·Polymers·Cătălina Natalia Cheaburu YilmazCătălina Elena Lupușoru
May 6, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Mikhail AgafonovIrina Terekhova

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