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ORIGINAL ARTICLES
Year : 2022  |  Volume : 11  |  Issue : 1  |  Page : 51-58

Synthesis, characterization, and cytotoxicity evaluation of methotrexate-polyethylene glycol-glutamic acid nanoconjugate as targeted drug delivery system in cancer treatment


1 Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
2 Department of Pharmaceutics, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
3 Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

Correspondence Address:
Prof. Katayoun Derakhshandeh
Department of Pharmaceutics, School of Pharmacy, Hamadan University of Medical Sciences, 8678-3-65178 Hamadan
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jrptps.JRPTPS_97_21

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Introduction: Methotrexate (MTX) is used as a folic acid antagonist in the treatment of many human cancers. Attachment of hydrophilic ligands to MTX improves its efficacy due to reducing toxicity and enzymatic degradation and it also increases its in-vivo half-life. Materials and Methods: In the present study, pH-responsive nanoconjugates of methoxy poly(ethylene glycol)-glutamic acid methotrexate (mPEG-Glu-MTX) have been prepared and characterized using hydrogen nuclear magnetic resonance (1H-NMR) and Fourier transform infrared (FT-IR). Glutamic acid is attached to the mPEG chain by the carboxylic group and to the MTX via an amide bond to the amine group. Results: The prepared nanoconjugate has the mean diameter ranging from 160 to 190 nm and, the drug release was significantly induced two times at the pH of 5.5 and 3.5 compared with pH 7.4 (P < 0.05). The prepared mPEG-Glu-MTX nanoconjugate showed toxicity similar to AGS, MDA, and MCF7 cell lines compared with the free form of MTX (P > 0.1), which indicates that the conjugation does not effect on the MTX cytotoxicity but is expected to be successful in the targeted delivery of MTX. Conclusion: The results show that manufactured nanoconjugates can be considered as an efficient drug delivery system in the treatment of cancer; however, further studies are needed on the targeting activity of this nanocarrier in in-vivo conditions.


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