Stiffness can mediate the balance between hydrodynamic forces and avidity to impact the targeting of flexible polymeric nanoparticles in flow

ORAL

Abstract

We report computational investigations of deformable polymeric nanoparticles (NPs) under colloidal suspension flow and adhesive environment. We employ a coarse-grained model for the polymeric NP and perform Brownian dynamics simulations with hydrodynamic interactions and in presence of wall-confinement, particulate margination, and wall-adhesion for obtaining NP microstructure, shape, and anisotropic and inhomogeneous transport properties for different NP stiffness. Comparing our computational results for the amount of NP margination to the near-wall adhesion regime with those of our binding experiments in cell culture under shear, as well as those of tissue targeting measurements in vivo in mice, we found quantitative agreement on shear-enhanced binding, effects of particulate volume fraction, and effects of NP stiffness. The reported combined computational approach and results are expected to enable fine-tuning of design and optimization of flexible NP in targeted drug delivery applications.

*We acknowledge support from the National Institutes of Health through grants 1R01EB006818, U01EB016027, and 1U54CA193417. Computational resources were provided in part by the Penn Bioengineering, MRSEC and by the Extreme Science and Engineering Discovery
Environment (XSEDE) grant MCB060006.

–

Presenters

  • Samaneh Farokhirad

    • Department of Mechanical and Industrial Engineering, New Jersey Institute of Technology

Authors

  • Samaneh Farokhirad

    • Department of Mechanical and Industrial Engineering, New Jersey Institute of Technology

  • Abhay Ranganathan

    • Department of Anesthesiology and Critical Care, University of Pennsylvania

  • Jacob Myerson

    • Department of Pharmacology, University of Pennsylvania

  • Vladimir R. Muzykantov

    • Department of Pharmacology, University of Pennsylvania,

  • Portonovo Ayyaswamy

    • Department of Mechanical and Aerospace Engineering, University of California, Los Angeles

  • David M. Eckmann

    • Department of Anesthesiology, Ohio State University

  • Ravi Radhakrishnan

    • Department of Chemical and Biomolecular Engineering, University of Pennsylvania