Preparation And Pharmacokinetics Of Arsenic Trioxide-PLGA-Nanoparticles

[Object]As₂O₃ bone marrow targeted nanoparticles were prepared and the particle size, entrapment rate and morphology are determined.Also the in vitro release and the distribution were studied,to evaluate the efficacy of targeting.[Method]The W/O/W double emulsion-solvent evaporation method was employed to prepare As₂O₃-PLGA-NP,while the PLGA was selected as carrier material.The morphology of nanoparticle was screened by TEM.The particle size was measured by particle size and Zeta Potential Analyzer.Free As₂O₃ was separated from nanoparticle with dynamic dialysis and choose atomic fluorescence method to measure the drug content and in vitro release of As₂O₃.The plasma samples of rats and tissue samples of mice were dissociated by heating. The pharmacokinetic parameters were calculated by 3P97 computer program.And nanoparticle distribution in mice was evaluated by DTI and DSI.[Results]The nanoparticle solution looks like transparent and weak blue in color,with a little opalescence.TEM gave the morphology of nanoparticle is spherical and irregular in form. The mean diameter of nanoparticle is about 80 nm or so.The mean entrapment rate of As₂O₃-PLGA-NP came to more than 80%.In vitro release test illuminated the drug release of PLGA nanoparticle is slow.The cumulative percentage of drug is nearly to 40%after i.v. administration 24h and to 45%after 48h.The pharmacokinetic parameters and distribution results of As₂O₃-PLGA-NP suggested that the metabolism speed of As₂O₃-PLGA-NP is slower than As₂O₃ normal solution and As₂O₃-PLGA-NP can really promote the drug content in bone marrow.[Conclusion]W/O/W double emulsion evaporation is a simple and feasible method.The As₂O₃-PLGA-NP is in small and homogeneous size,good morphology and high entrapment rate.Drug released slowly and no burst release.As₂O₃-PLGA-NP could prolong the elimination half-life time in rats markedly,also it can increase the drug distribution in bone marrow of mice and reduce the drug distribution in liver.