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

IF 0.7 Q4 PHARMACOLOGY & PHARMACY
M. Ahmadi, K. Derakhshandeh, Abbas H Azandaryani, H. Adibi
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引用次数: 0

Abstract

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.
癌症靶向给药系统甲氨蝶呤-聚乙二醇-谷氨酸纳米复合物的合成、表征及细胞毒性评价
简介:甲氨蝶呤(MTX)被用作叶酸拮抗剂,用于治疗许多人类癌症。亲水性配体附着在MTX上,由于降低毒性和酶降解,提高了其功效,也增加了其体内半衰期。材料与方法:制备了甲氧基聚乙二醇-谷氨酸甲氨甲酸(mPEG-Glu-MTX)的ph响应纳米偶联物,并利用氢核磁共振(1H-NMR)和傅里叶变换红外(FT-IR)对其进行了表征。谷氨酸通过羧基连接到mPEG链上,并通过酰胺键连接到胺基上。结果:制备的纳米偶联物的平均直径为160 ~ 190 nm,在pH为5.5和3.5时较pH为7.4时显著诱导药物释放(P < 0.05)。与游离形式的MTX相比,制备的mPEG-Glu-MTX纳米偶联物显示出与AGS, MDA和MCF7细胞系相似的毒性(P > 0.1),这表明该偶联物不影响MTX的细胞毒性,但有望成功用于MTX的靶向递送。结论:制备的纳米缀合物可作为治疗肿瘤的有效药物传递系统;然而,该纳米载体在体内的靶向活性还有待进一步研究。
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来源期刊
Journal of Reports in Pharmaceutical Sciences
Journal of Reports in Pharmaceutical Sciences Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)
CiteScore
1.40
自引率
0.00%
发文量
0
期刊介绍: The Journal of Reports in Pharmaceutical Sciences(JRPS) is a biannually peer-reviewed multi-disciplinary pharmaceutical publication to serve as a means for scientific information exchange in the international pharmaceutical forum. It accepts novel findings that contribute to advancement of scientific knowledge in pharmaceutical fields that not published or under consideration for publication anywhere else for publication in JRPS as original research article. all aspects of pharmaceutical sciences consist of medicinal chemistry, molecular modeling, drug design, pharmaceutics, biopharmacy, pharmaceutical nanotechnology, pharmacognosy, natural products, pharmaceutical biotechnology, pharmacology, toxicology and clinical pharmacy.
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