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Synthesis of galactosylated chitosan/5-fluorouracil nanoparticles and its characteristics, in vitro and in vivo release studies
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Biodegradable polymer nanoparticle drug delivery systems are characterized by targeted drug delivery, improved pharmacokinetic and biodistribution, enhanced drug stability, and lowered side effects; these drug delivery systems are widely used for delivery of cytotoxic agents. The galactosylated chitosan (GC)/5-fluorouracil (5-FU) nanoparticle is a nanomaterial made by coupling GC, a polymer known to have the advantages described above, and 5-FU. We found that when 5-FU and GC were mixed at the mass ratio of 10:1, the nanoparticle reached a maximum encapsulation efficiency of 81.82% ± 5.32%, with a drug loading of 6.12% ± 1.36%, a particle size of 35.19 ± 9.50 nm, and a Zeta potential of +10.34 ± 1.43 mV. The GC/5-FU nanoparticle is a sustained release system, whose anticancer effects were shown to be dose and time dependent, with a higher cytotoxicity to hepatic cancer than to other cell types. The distribution of GC/5-FU in vivo revealed the greatest accumulation in the hepatic cancer tissues, with an 8.69-, 23.35-, 79.96-, and 85.15-fold increase when compared to normal liver tissue, kidney, heart and blood, respectively, suggesting that the hepatic cell was the target of the nanoparticles. In vivo experiments showed that GC/5-FU can significantly inhibit tumor growth in an orthotropic liver cancer mouse model. GC/5-FU treatment can significantly lower the tumor weight and increase the survival time of mice when compared to 5-FU treatment alone. Flow cytometry revealed that compared to 5-FU, GC/5-FU caused higher rates of G0–G1 arrest and apoptosis in hepatic cancer cells.
This study describes the preparation of galactosylated chitosan (GC)/5-fluorouracil (5-FU) nanoparticles and characterization studies for this nanoparticle, including the distribution of GC/5-FU.
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Journal of Biomedical Materials Research Part B, 100B(8): 2035-2043 (November 2012)
Journal of Biomedical Materials Research Part B: Applied Biomaterials
Cheng M, Han J, Li Q, He B, Zha B, Wu J, Zhou R, Ye T, Wang W, Xu H, Hou Y
Last updated on October 18, 2012
This work is supported in part by the Nanoscale Science and Engineering Initiative of the National Science Foundation
under NSF Award Number EEC-0118007.
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