Advertisement

A model predicting delivery of saquinavir in nanoparticles to human monocyte/macrophage (Mo/Mac) cells

Authors

  • D. Ece Gamsiz,

    1. Department of Chemical Engineering, 342 Snell Engineering Center, 360 Huntington Avenue, Northeastern University, Boston, Massachusetts 02115; telephone: 617-373-7126;fax: 617-373-2209
    Search for more papers by this author
  • Lipa K. Shah,

    1. Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts
    Current affiliation:
    1. Novartis Institutes for BioMedical Research, Cambrige, MA.
    Search for more papers by this author
    • Assistant Professor.

  • Harikrishna Devalapally,

    1. Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts
    Search for more papers by this author
  • Mansoor M. Amiji,

    1. Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts
    Search for more papers by this author
  • Rebecca L. Carrier

    Corresponding author
    1. Department of Chemical Engineering, 342 Snell Engineering Center, 360 Huntington Avenue, Northeastern University, Boston, Massachusetts 02115; telephone: 617-373-7126;fax: 617-373-2209
    • Department of Chemical Engineering, 342 Snell Engineering Center, 360 Huntington Avenue, Northeastern University, Boston, Massachusetts 02115; telephone: 617-373-7126;fax: 617-373-2209.
    Search for more papers by this author

Abstract

Modeling the influence of a technology such as nanoparticle systems on drug delivery is beneficial in rational formulation design. While there are many studies showing drug delivery enhancement by nanoparticles, the literature provides little guidance regarding when nanoparticles are useful for delivery of a given drug. A model was developed predicting intracellular drug concentration in cultured cells dosed with nanoparticles. The model considered drug release from nanoparticles as well as drug and nanoparticle uptake by the cells as the key system processes. Mathematical expressions for these key processes were determined using experiments in which each process occurred in isolation. In these experiments, intracellular delivery of saquinavir, a low solubility drug dosed as a formulation of poly(ethylene oxide)-modified poly(epsilon- caprolactone) (PEO–PCL) nanoparticles, was studied in THP-1 human monocyte/macrophage (Mo/Mac) cells. The model accurately predicted the enhancement in intracellular concentration when drug was administered in nanoparticles compared to aqueous solution. This simple model highlights the importance of relative kinetics of nanoparticle uptake and drug release in determining overall enhancement of intracellular drug concentration when dosing with nanoparticles. Biotechnol. Bioeng. © 2008 Wiley Periodicals, Inc.

Ancillary