title: 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.
authors.affiliation: Department of General Surgery, Zhoupu Hospital of Shanghai Pudong New Area, Shanghai 201318, China. cmrlq@126.com
authors.forename: Mingrong
authors.initials: M
authors.lastname: Cheng
authors.forename: Jiang
authors.initials: J
authors.lastname: Han
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.forename: Bingbing
authors.initials: B
authors.lastname: Zha
authors.forename: Jingbo
authors.initials: J
authors.lastname: Wu
authors.forename: Runjiao
authors.initials: R
authors.lastname: Zhou
authors.forename: Tao
authors.initials: T
authors.lastname: Ye
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Xu
authors.forename: Yiming
authors.initials: Y
authors.lastname: Hou
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects
chemical_list: D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D048271:Chitosan; D005472:Fluorouracil