Studies On Preparation And Targeting Characteristics Of Arsenic Trioxide-polylactic-co-glycolic Acid Nanoparticles(As₂O₃-PLGA-NP)

Objective:The arsenic trioxide- polylactic-co-glycolic acid nanoparticles (As₂O₃ -PLGA -NP)were prepared by optimal technological procedure,its distribution and pharmacokinetics characteristics were investigated with animal experiments.Methods: 1. As₂O₃-PLGA-NP were prepared by w/o/w double-emulsion evaporation technique.Various factors related with the entrapment ratio and nanoparticle diameter were studied.The uniform experimental design U₁₅ (15⁵) was chosen to optimize the preparation technology of nanoparticles.The particle diameter,surface morphology,release property in vitro and stability of the optimized nanoparticles colloid were evaluated by electron microscopy,release test in vitro and stability test.2.100 mice,weight 20-25g,were divided randomly into 20 groups,and 5 mice each group,which were injected As₂O₃-PLGA-NP or As₂O₃ at the dose of 2mg/kg in candal vein.At different times after injection ,the lung,liver,kidney,spleen and heart were rapidly removed, arsenic concerntration in tissues respectively were measured by hydride generation atomic fluorometry spectrophotometry(HG-AFS). Pharmacokinetic characteristics of As₂O₃-PLGA-NP and As₂O₃ in liver of mice were analyzed by PKS computer programs.3.6 rabbits,weight 2.3-2.5kg,with cross-over design were injected As₂O₃-PLGA-NP or As₂O₃ at the dose of 1mg/kg.The arsenic concerntration in plasma were measured by HG-AFS at different times after injection.Pharmacokinetic characteristics of As₂O₃-PLGA- NP and As₂O₃ in plasma of rabbits were analyzed by PKS computer programs. Results:1. As₂O₃-PLGA-NP were prepared by w/o/w double-emulsion evaporation technique with emulsion by ultrasonic,then evaporating at room temperature for 3 hours.The factors that influence the nanoparticles entrapment ratio and diameter was investigated.The analysis showed (1)drug/polymer;(2) polymer concentration;(3) ultrasonic intensity;(4)PVA concentration,which were the main factors that influence the entrapment ratio of As₂O₃-PLGA-NP.Under the optimal manufacture conditions, As₂O₃ was entrapped 53.19±1.82%,the drug loading was 0.64±0.02%,the mean diameter of the obtained...