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The In Vitro Anti-Tumor Efficacy and the Pharmacokinetics of N3-O-Toluyl-Fluorouracil Loaded Nanosuspension (TFu-LNS)

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N3-o-toluyl-fluorouracil (TFu) was a potent water-insoluble prodrug of 5-fuorouracil (5-Fu). To improve the solubility of TFu, TFu loaded nanosuspension (TFu-LNS) was prepared by high-pressure homogenization method. The results of in vitro release studies showed that 5-Fu was sustained released from TFu-LNS. Then in vitro antitumor activity of TFu-LNS in terms of antiproliferative activity, induction of apoptosis and G1 cycle arrest on human breast adenocarcinoma cell line (MCF-7) and human gastric carcinoma cell line (BGC) was evaluated. The results of MTT assay showed that TFu-LNS exhibited higher antiproliferative activity against MCF-7 and BGC cells than TFu DMSO-water solution and 5-Fu solution. The apoptosis induced by TFu-LNS was assessed by Annexin V-FITC/PI double staining and Tunnel assay. And the results of two methods both clearly indicated that the superiority of TFu-LNS to TFu DMSO-water solution and 5-Fu solution in increasing the apoptosis rate of MCF-7 and BGC cells. The results of flow cytometric (FCM) analysis demonstrated that TFu-LNS could induce G1 cycle arrest of MCF-7 and BGC cells. Furthermore, in vivo pharmacokinetics study in Wistar rats indicated that TFu-LNS was capable of increasing the parameters of AUC(0- and MRT significantly by sustained releasing 5-Fu. Therefore, the overall results suggested that the TFu-LNS could enhance anti-tumor effect and hold great potential to be developed for cancer treatments.
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Document Type: Research Article

Publication date: May 1, 2013

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  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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