title: Stable loading and delivery of disulfiram with mPEG-PLGA/PCL mixed nanoparticles for tumor therapy.
abstract: Disulfiram (DSF) showed great potential in an in vitro tumor therapy study; however, those results could not be applied to an in vivo study due to the extreme instability of DSF in blood. Here, we describe a system of methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide)/poly(ε-caprolactone) (mPEG-PLGA/PCL) mixed nanoparticles (NPs) for DSF loading and delivery. By adjusting the mPEG-PLGA/PCL content ratios, the DSF loading capacity increased to 7.8%, while the hydrodynamic radii of the NPs were around 50-100nm. The DSF-loaded NPs showed high stability in distilled water and 10% serum-containing phosphate buffered saline. The NPs efficiently protected DSF from degradation while maintaining its anti-tumor properties. Furthermore, a pharmacokinetics study demonstrated that NP delivery system enhanced the DSF concentration in the blood after tail vein injection. Finally, DSF delivery using this model effectively slowed the growth of a 4T1 murine xenograft tumor.
  
  
  BACKGROUND
  The anti-tumor efficacy of the anti-alcoholic drug disulfiram has been known for some time. However, its use in the clinical setting is limited due to the underlying instability of the drug. In this study, the authors utilized a nanocarrier system of mPEG-PLGA/PCL for the delivery of this drug. The promising results may allow encapsulation of other drugs.
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, PR China.
authors.forename: Wantong
authors.initials: W
authors.lastname: Song
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, PR China. Electronic address: ztang@ciac.ac.cn.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China.
authors.forename: Tian
authors.initials: T
authors.lastname: Lei
authors.affiliation: Department of Chemistry, Northeast Normal University, Changchun, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wen
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, PR China.
authors.forename: Guanyi
authors.initials: G
authors.lastname: Wang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, PR China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Northeast Normal University, Changchun, PR China.
authors.forename: Mingxiao
authors.initials: M
authors.lastname: Deng
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China. Electronic address: tangpharm@sina.com.
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, PR China. Electronic address: xschen@ciac.ac.cn.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D065086:Acetaldehyde Dehydrogenase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D000427:Alcohol Deterrents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D001940:Breast / Q000187:drug effects / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004221:Disulfiram / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D017207:Rats, Sprague-Dawley
chemical_list: D065086:Acetaldehyde Dehydrogenase Inhibitors; D000427:Alcohol Deterrents; D000970:Antineoplastic Agents; D004337:Drug Carriers; D011091:Polyesters; C558447:methoxypolyethyleneglycol-poly(lactic-co-glycolic acid); C016240:polycaprolactone; D011092:Polyethylene Glycols; D004221:Disulfiram
keywords: Disulfiram; Drug delivery; Nanoparticles; PCL; mPEG-PLGA