title: Long-circulating Janus nanoparticles made by electrohydrodynamic co-jetting for systemic drug delivery applications.
abstract: BACKGROUND
  Nanoparticles with controlled physical properties have been widely used for controlled release applications. In addition to shape, the anisotropic nature of the particles can be an important design criterion to ensure selective surface modification or independent release of combinations of drugs.
  
  
  OBJECTIVE
  Electrohydrodynamic (EHD) co-jetting is used for the fabrication of uniform anisotropic nanoparticles with individual compartments and initial physicochemical and biological characterization is reported.
  
  
  METHODS
  EHD co-jetting is used to create nanoparticles, which are characterized at each stage with scanning electron microscopy (SEM), structured illumination microscopy (SIM), dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). Surface immobilization techniques are used to incorporate polyethylene glycol (PEG) and I(125) radiolabels into the nanoparticles. Particles are injected in mice and the particle distribution after 1, 4 and 24 hours is assessed.
  
  
  CONCLUSIONS
  Nanoparticles with an average diameter of 105.7 nm are prepared by EHD co-jetting. The particles contain functional chemical groups for further surface modification and radiolabeling. The density of PEG molecules attached to the surface of nanoparticles is determined to range between 0.02 and 6.04 ligands per square nanometer. A significant fraction of the nanoparticles (1.2% injected dose per mass of organ) circulates in the blood after 24 h.
  
  
  CONCLUSIONS
  EHD co-jetting is a versatile method for the fabrication of nanoparticles for drug delivery. Circulation of the nanoparticles for 24 h is a pre-requisite for subsequent studies to explore defined targeting of the nanoparticles to a specific anatomic site.
authors.affiliation: a Biointerfaces Institute, University of Michigan , Ann Arbor , MI , USA .|b Biomedical Engineering, University of Michigan , Ann Arbor , MI , USA .|c Institute of Functional Interfaces (IFG), Karlsruhe Institute of Technology (KIT) , Germany .
authors.forename: Sahar
authors.initials: S
authors.lastname: Rahmani
authors.affiliation: d Department of Pharmacology , University of Pennsylvania , Philadelphia , PA , USA , and.
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Villa
authors.affiliation: a Biointerfaces Institute, University of Michigan , Ann Arbor , MI , USA .
authors.forename: Acacia F
authors.initials: AF
authors.lastname: Dishman
authors.affiliation: a Biointerfaces Institute, University of Michigan , Ann Arbor , MI , USA .|b Biomedical Engineering, University of Michigan , Ann Arbor , MI , USA .
authors.forename: Marika E
authors.initials: ME
authors.lastname: Grabowski
authors.affiliation: d Department of Pharmacology , University of Pennsylvania , Philadelphia , PA , USA , and.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Pan
authors.affiliation: a Biointerfaces Institute, University of Michigan , Ann Arbor , MI , USA .|e Department of Chemical Engineering , University of Michigan , Ann Arbor , MI , USA.
authors.forename: Hakan
authors.initials: H
authors.lastname: Durmaz
authors.affiliation: a Biointerfaces Institute, University of Michigan , Ann Arbor , MI , USA .|b Biomedical Engineering, University of Michigan , Ann Arbor , MI , USA .
authors.forename: Asish C
authors.initials: AC
authors.lastname: Misra
authors.affiliation: a Biointerfaces Institute, University of Michigan , Ann Arbor , MI , USA .|e Department of Chemical Engineering , University of Michigan , Ann Arbor , MI , USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Colón-Meléndez
authors.affiliation: a Biointerfaces Institute, University of Michigan , Ann Arbor , MI , USA .|e Department of Chemical Engineering , University of Michigan , Ann Arbor , MI , USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Solomon
authors.affiliation: d Department of Pharmacology , University of Pennsylvania , Philadelphia , PA , USA , and.
authors.forename: Vladimir R
authors.initials: VR
authors.lastname: Muzykantov
authors.affiliation: a Biointerfaces Institute, University of Michigan , Ann Arbor , MI , USA .|b Biomedical Engineering, University of Michigan , Ann Arbor , MI , USA .|c Institute of Functional Interfaces (IFG), Karlsruhe Institute of Technology (KIT) , Germany .|e Department of Chemical Engineering , University of Michigan , Ann Arbor , MI , USA.
authors.forename: Joerg
authors.initials: J
authors.lastname: Lahann
mesh_terms: D000818:Animals; D016880:Anisotropy; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D000067493:Dynamic Light Scattering; D057446:Hydrodynamics; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D003692:Delayed-Action Preparations; D007457:Iodine Radioisotopes; D011108:Polymers; D011092:Polyethylene Glycols
keywords: Biodistribution studies; Janus nanoparticles; electrospraying; functional polymers; ligand density