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The in vitro anti-tumor efficacy and the pharmacokinetics of N3-o-toluyl-fluorouracil loaded nanosuspension (TFu-LNS).
- Source :
-
Journal of biomedical nanotechnology [J Biomed Nanotechnol] 2013 May; Vol. 9 (5), pp. 801-10. - Publication Year :
- 2013
-
Abstract
- 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-infinity) 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.
- Subjects :
- Animals
Antineoplastic Agents administration & dosage
Cell Line, Tumor
Cell Proliferation drug effects
Fluorouracil administration & dosage
Fluorouracil pharmacokinetics
Humans
Male
Materials Testing
Mice
Microsomes, Liver enzymology
Microsomes, Liver metabolism
Prodrugs administration & dosage
Rats
Rats, Wistar
Solubility
Suspensions
Treatment Outcome
Xenograft Model Antitumor Assays
Antineoplastic Agents pharmacokinetics
Fluorouracil analogs & derivatives
Nanostructures administration & dosage
Nanostructures chemistry
Prodrugs pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1550-7033
- Volume :
- 9
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of biomedical nanotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 23802409
- Full Text :
- https://doi.org/10.1166/jbn.2013.1586