Synthesis of galactosylated chitosan/5‐fluorouracil nanoparticles and its characteristics, in vitro and in vivo release studies

Abstract 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. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.