Folic acid-decorated and PEGylated PLGA nanoparticles for improving the antitumour activity of 5-fluorouracil

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• 作者：Mazen M. El-Hammadi^a ; ^b ; Á ; ngel V. Delgado^c ; Consolació ; n Melguizo^d ; ^e ; José ; C. Prados^d ; ^e ; José ; L. Arias^a ; ^d ; ^e ; ^{jlarias@ugr.es}
• 关键词：Cancer chemotherapy ; 5-Fluorouracil ; FOL-PEG-PLGA conjugate ; Haemocompatibility ; Ligand-receptor mediated drug delivery ; Nanoprecipitation.
• 刊名：International Journal of Pharmaceutics
• 出版年：2017
• 出版时间：10 January 2017
• 年：2017
• 卷：516
• 期：1-2
• 页码：61-70
• 全文大小：1596 K
• 卷排序：516

文摘

5-Fluorouracil (5-FU) is a broad spectrum cytotoxic agent being used in chemotherapy of malignancies. However, 5-FU shows a number of limitations like short half-life, non-selective biodistribution, and the development of drug resistances by tumour cells. It was investigated the potential use of folic acid-decorated and PEGylated poly(D,L-lactide-co-glycolide) nanoparticles (FOL-PEG-PLGA NPs) for the targeted delivery of 5-FU to colon and breast cancers. PEG-PLGA and FOL-PEG-PLGA conjugates were synthesized and characterized. NPs of PLGA, PEG-PLGA, and FOL-PEG-PLGA were prepared by nanoprecipitation under optimal formulation conditions. They were found to be haemocompatible, and exhibited negligible cytotoxicity in normal (CCD-18 and MCF-10A) and tumour (HT-29 and MCF-7) human cell lines. 5-FU loading capabilities were also defined, and the NPs exhibited an initial burst drug release followed by a sustained 5-FU release. In vitro cytotoxicity studies in folate-overexpressed HT-29 colon cancer cells and MCF-7 breast cancer cells demonstrated that the half maximal inhibitory concentration (IC50) of 5-FU-loaded FOL-PEG-PLGA NPs was approximately 4-fold less than that of the 5-FU-loaded PLGA NPs (p < 0.05). Consequently, FOL-PEG-PLGA NPs could have great potential as a targeted 5-FU delivery system for colon and breast cancer treatment.