title: Directed self-assembled nanoparticles of probucol improve oral delivery: fabrication, performance and correlation.
abstract: OBJECTIVE
  We are reporting on the development of a unique drug delivery platform by directed self-assembly technique to improve the oral delivery of hydrophobic drugs.
  
  
  METHODS
  Herein, a series of probucol directed self-assembled nanoparticles (PDN) were developed with two components of probucol and surfactant such as Tween 20, Tween 80, D-alpha-tocopheryl polyethylene glycol 1,000 succinate (TPGS) and HS-15, which was respectively named as T20-PDN, T80-PDN, TP-PDN and HS-PDN. The formation of various PDNs was determined by in vitro characterization and the physicochemical properties of these PDNs were determined. Moreover, the performance of PDN in enhancing the oral delivery and possible correlation between the in vitro properties and in vivo performances were investigated.
  
  
  RESULTS
  PDN was homogenous nanometer-sized particles with negative surface charge. The cellular uptake of probucol in Caco-2 cell monolayer was respectively increased 1.15, 1.82, 1.59 and 5.31-fold by these PDN. In particular, the oral bioavailability of these PDN was significantly improved 3.0, 4.1, 5.4 and 10.4 folds compared with the free drug suspension. The enhanced cellular uptake and oral bioavailability were correlated with the characters of involved surfactants and the particle size of PDN.
  
  
  CONCLUSIONS
  Thereby, the directed self-assembled nanoparticles could provide a new strategy for enhancing the oral delivery of hydrophobic drugs.
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Shijun
authors.initials: S
authors.lastname: Jiang
authors.forename: Zeying
authors.initials: Z
authors.lastname: Liu
authors.forename: Baohua
authors.initials: B
authors.lastname: Niu
authors.forename: Wangwen
authors.initials: W
authors.lastname: Gu
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
authors.forename: Jingbin
authors.initials: J
authors.lastname: Cui
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D018938:Caco-2 Cells; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D011341:Probucol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017207:Rats, Sprague-Dawley; D013501:Surface-Active Agents / Q000737:chemistry; D014810:Vitamin E / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D000924:Anticholesteremic Agents; D004337:Drug Carriers; D011136:Polysorbates; D013501:Surface-Active Agents; D014810:Vitamin E; D011092:Polyethylene Glycols; C014225:tocophersolan; D011341:Probucol