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Original Article

Long-circulating Janus nanoparticles made by electrohydrodynamic co-jetting for systemic drug delivery applications

Sahar RahmaniBiointerfaces Institute, University of Michigan, Ann Arbor, MI, USA, ;Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA, ;Institute of Functional Interfaces (IFG), Karlsruhe Institute of Technology (KIT), Germany,

Carlos H. VillaDepartment of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA, and

Acacia F. DishmanBiointerfaces Institute, University of Michigan, Ann Arbor, MI, USA,

Marika E. GrabowskiBiointerfaces Institute, University of Michigan, Ann Arbor, MI, USA, ;Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA,

Daniel C. PanDepartment of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA, and

Hakan DurmazBiointerfaces Institute, University of Michigan, Ann Arbor, MI, USA, ;Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA

Asish C MisraBiointerfaces Institute, University of Michigan, Ann Arbor, MI, USA, ;Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA,

Laura Colón-MeléndezBiointerfaces Institute, University of Michigan, Ann Arbor, MI, USA, ;Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA

Michael J. SolomonBiointerfaces Institute, University of Michigan, Ann Arbor, MI, USA, ;Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA

Vladimir R. MuzykantovDepartment of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA, and

Joerg LahannBiointerfaces Institute, University of Michigan, Ann Arbor, MI, USA, ;Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA, ;Institute of Functional Interfaces (IFG), Karlsruhe Institute of Technology (KIT), Germany, ;Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USACorrespondence[email protected]

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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.

Purpose: 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 I¹²⁵ radiolabels into the nanoparticles. Particles are injected in mice and the particle distribution after 1, 4 and 24 hours is assessed.

Results and discussion: 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.

Conclusion: 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.

Keywords

Declaration of Interest

The authors would like to acknowledge funding from the Multidisciplinary University Research Initiative of the Department of Defense and the Army Research Office (W911NF-10-1-0518), the DOD through an idea award (W81XWH-11-1-0111), the Tissue Engineering and Regenerative Medicine Training Grant (DE00007057-36), and the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 310445 (SAVVY).

Supplementary material available online.

Supplemental Figure S1.

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Long-circulating Janus nanoparticles made by electrohydrodynamic co-jetting for systemic drug delivery applications

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Long-circulating Janus nanoparticles made by electrohydrodynamic co-jetting for systemic drug delivery applications

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