# Physiologically Based Pharmacokinetic Modeling of Silica Nanoparticles

> **NIH NIH R03** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $81,119

## Abstract

PROJECT SUMMARY
Silica nanoparticles are multifunctional and biocompatible inorganic nanocarriers with enormous potential for
drug delivery. Their unique structural composition and porosity facilitates the loading of large therapeutic
payloads for site-specific drug delivery. Since past two decades our team characterized silica nanoparticles
and obtained data on cellular uptake, pharmacokinetics, and toxicity in rodents. However, very little is known
about pharmacokinetics and biodistribution of silica nanoparticles in humans. A better understanding of the
pharmacokinetics of silica nanoparticles in humans is essential for their clinical translation. Physiologically
based pharmacokinetic (PBPK) modeling is well established strategy to translate mechanistic knowledge from
animals to humans. We propose to develop PBPK models of silica nanoparticles in mice and rats and
extrapolate them to humans to establish a relationship between organ accumulation, and human dose. PBPK
models integrate compound specific data with physiology of the organism to predict the pharmacokinetics of
drugs. PBPK models are mechanistic and can account for complex in vivo transport mechanisms of
nanoparticles such as opsonization, mononuclear phagocyte system uptake, lymphatic transport, and cellular
internalization. Once the predictive performance of nanoparticle PBPK models in preclinical models is verified,
the mechanisms governing nanoparticle PK can be easily extrapolated to humans by replacing relevant
physiological information. The final human nanoparticle PBPK model extrapolated from animals can be used
for first-in-human predictions. There are no PBPK models available for silica nanoparticles that can incorporate
all relevant properties required for extrapolation to humans. Our long-term goal is to successfully translate
silica nanoparticles to human clinical use as drug delivery vehicles. The objective of this proposal is to translate
the mechanisms of nanoparticle distribution from rodents to humans. The Specific Aims of the proposal are: 1)
Develop and validate PBPK models for various silica nanoparticles in mice and rats, 2) Extrapolate the rodent
PBPK model of silica nanoparticles to humans and verify the predictions using clinical data. The proposed
research addresses a significant unmet need for evaluating the relationship between dose and organ
accumulation of silica nanoparticles in humans. Our research project is innovative because we use
mathematical modeling and simulation techniques that use data obtained from our laboratory studies and
published literature. The data obtained from this research project will be used for submitting an R01 application
to develop and validate PBPK models for silica nanoparticles with drugs and macromolecules. The PBPK
models for the R01 proposal will include larger animal species such as dogs and rabbits.

## Key facts

- **NIH application ID:** 10508729
- **Project number:** 1R03EB033576-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Venkata K Yellepeddi
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $81,119
- **Award type:** 1
- **Project period:** 2022-09-06 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10508729

## Citation

> US National Institutes of Health, RePORTER application 10508729, Physiologically Based Pharmacokinetic Modeling of Silica Nanoparticles (1R03EB033576-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10508729. Licensed CC0.

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