PBPK Modeling of the Nanoparticle Biodistribution: Interspecies Extrapolation and Tumor Targeting

Mingguang Li1, Joshua Reineke1

1Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, 48202, USA

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Summary
Polymeric nanoparticles have been widely investigated for the delivery of therapeutics, especially for chemotherapy. The majority of nanoparticle studies are carried out in animal models with the expectation to be applied to humans. However, the interspecies variability of nanoparticle biodsitribution is largely neglected. The effects of physiological and pathological conditions need to be further understood.

By using Physiologically Based Pharmacokinetic (PBPK) modeling, we simulated the experimental data of PLGA nanoparticle biodistribution in mice and calculated the kinetic rate constants of the major organs and a solid primary tumor. The model was then used to extrapolate biodistribution into other species including human. Further, we explored this model function in dose selection and tumor targeting.

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