# Physiologically based pharmacokinetic modeling and analysis of administration route-dependent tissue distribution of gold nanoparticles

> **NIH NIH R03** · UNIVERSITY OF FLORIDA · 2020 · $76,250

## Abstract

PROJECT SUMMARY AND ABSTRACT
Gold nanoparticles have found promising applications as drug carriers for diagnostic and therapeutic purposes
in laboratory animals, but the translation of animal results to clinical success is low. Currently, this field is
confronting a dilemma of “so many publications but very few drugs”. There are multiple factors contributing to
this. One important factor is a lack of a robust model that can integrate available experimental data to simulate
target organ dosimetry and extrapolate pharmacokinetics of gold nanoparticles across different exposure
scenarios. Another critical factor is that the traditional pharmacokinetic analysis approaches currently used for
small molecules (e.g., drugs and environmental chemicals) are used for nanoparticles, which may not be
appropriate because of differences in the pharmacokinetics between small molecules and nanoparticles. Built
upon the extensive pharmacokinetic datasets for different sizes of gold nanoparticles in rats after different routes
of administration (i.e., intravenous injection, oral gavage, inhalational exposure, or intratracheal instillation) from
our collaborator’s laboratory and based on our recently published physiologically based pharmacokinetic (PBPK)
model for gold nanoparticles after single route of intravenous administration, here we propose a multi-route
whole-body PBPK modeling strategy to address these challenges. The objective of this proposal is to determine
whether the traditional route-to-route extrapolation approaches of PBPK models for small molecules are
appropriate for gold nanoparticles. We hypothesize that the traditional route-to-route extrapolation approaches
of PBPK models for small molecules may not be appropriate for gold nanoparticles. Two Specific Aims were
formulated to test this hypothesis. Aim 1: To develop a multi-route PBPK model for gold nanoparticles using
traditional PBPK modeling approaches that are typically used for small molecules. Aim 2: To develop a multi-
route PBPK model for gold nanoparticles using a new approach particularly designed for nanoparticles. This
project is novel and significant because the route-to-route extrapolation of nanoparticle pharmacokinetics has
not been rigorously and quantitatively tested before and represents a critical barrier in the field. The proposed
research has broad impacts because: (1) if the aims are achieved and our hypothesis is true, then it will establish
a rational approach for conducting route-to-route extrapolation that is specifically for nanoparticles; (2) if the
results suggest that our hypothesis is false, then at minimal a new robust multi-route PBPK model will be
established and our results will greatly improve our fundamental understanding of route-dependent tissue
distribution of gold nanoparticles; (3) the proposed PBPK models will be converted to a graphical user interface
(GUI) that will be shared with other researchers, thereby making a wide impact in the field by allowin...

## Key facts

- **NIH application ID:** 10450369
- **Project number:** 7R03EB026045-03
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Zhoumeng Lin
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $76,250
- **Award type:** 7
- **Project period:** 2019-09-10 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450369

## Citation

> US National Institutes of Health, RePORTER application 10450369, Physiologically based pharmacokinetic modeling and analysis of administration route-dependent tissue distribution of gold nanoparticles (7R03EB026045-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10450369. Licensed CC0.

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