Abstract:

BACKGROUND: Arsenic trioxide (As₂O₃) as an anticancer drug has obvious side-effect, however, no good method has been found to reduce As2O3 side effects.
OBJECTIVE: To assay whether As₂O₃ loaded chitosan nanoparticles (NPCS-As₂O₃) could delay releasing time, could prolong As2O3 duration time and reduce As₂O₃ drug side-effect.
METHODS: Twenty SD rats were evenly divided into As₂O₃ group and NPCS-As₂O₃ group for pharmacokinetics determination, the blood concentrations of arsenic were detected before and after the medicine treatment at different time points. For drug toxicology assay, 40 SD rats were evenly divided into four groups, namely As₂O₃ group, NPCS-As₂O₃ group, NPCS group and normal sodium group. The alanine aminotransferase, aspertate aminotransferase, creatine kinase, creatinine, urea nitrogen level in plasma were tested. The heart, liver, kidney toxicity of NPCS-As₂O₃ was observed through morphological observation of hematoxylin-eosin staining.
RESULTS AND CONCLUSION: NPCS-As₂O₃ significantly prolonged the half-life compared with the As₂O₃ (P < 0.05). Except for creatine kinase, plasma biochemical indicators of As₂O₃ group were statistically significant higher than any other group (P < 0.05). There was no statistically significance between plasma biochemical indicators of NPCS-As₂O₃ group with the same As₂O₃ plasma concentration and NPCS group and normal sodium group (P > 0.05). The liver and kidney showed obvious pathological changes in As2O3 group, while no morphology change was seen in NPCS-As₂O₃ group. In the four groups, the hearts all had no distinct morphological change. NPCS-As₂O₃ has delayed the drug release, prolonged the drug effective time and reduced the toxicity of As₂O₃ in vivo.