Quantitative Evaluation of Dendritic Nanoparticles in Mice: Biodistribution Dynamics and Downstream Tumor Efficacy Outcomes

Research output: Contribution to journalJournal articleResearchpeer-review

  • Christina Vasalou
  • Douglas Ferguson
  • Weimin Li
  • Victorine Muse
  • Francis D. Gibbons
  • Silvia Sonzini
  • Guangnong Zhang
  • Petar Pop-Damkov
  • Eric Gangl
  • Srividya B. Balachander
  • Shenghua Wen
  • Alwin G. Schuller
  • Sanyogitta Puri
  • Mariarosa Mazza
  • Marianne Ashford
  • Adrian J. Fretland
  • Dermot F. McGinnity
  • Rhys D. O. Jones
A physiologically based pharmacokinetic model was developed to describe the tissue distribution kinetics of a dendritic nanoparticle and its conjugated active pharmaceutical ingredient (API) in plasma, liver, spleen, and tumors. Tumor growth data from MV-4-11 tumor-bearing mice were incorporated to investigate the exposure/efficacy relationship. The nanoparticle demonstrated improved antitumor activity compared to the conventional API formulation, owing to the extended released API concentrations at the site of action. Model simulations further enabled the identification of critical parameters that influence API exposure in tumors and downstream efficacy outcomes upon nanoparticle administration. The model was utilized to explore a range of dosing schedules and their effect on tumor growth kinetics, demonstrating the improved antitumor activity of nanoparticles with less frequent dosing compared to the same dose of naked APIs in conventional formulations.
Original languageEnglish
JournalMolecular Pharmaceutics
Issue number1
Pages (from-to)172-187
Publication statusPublished - 2022

    Research areas

  • nanoparticles, dendrimers, biodistribution, modeling and simulation, tumor growth kinetics

ID: 288114045