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Physiologically Based Pharmacokinetic Modeling of Extracellular Vesicles
Prashant Kumar1, Darshan Mehta1, John J Bissler2
1Division of Biochemical Toxicology, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, AR 72079, USA.
Biology
|September 28, 2023
Summary
Physiologically based pharmacokinetic (PBPK) modeling predicts the absorption, distribution, metabolism, and excretion of extracellular vesicles (EVs). This approach optimizes EV-based drug delivery systems for enhanced therapeutic efficacy and safety in clinical applications.
Area of Science:
- Biomedical Engineering
- Pharmacology
- Nanotechnology
Background:
- Extracellular vesicles (EVs) are crucial for intercellular communication and implicated in diseases like cancer.
- EVs show promise as drug delivery platforms due to their protective and targeting capabilities.
- Advancements in EV research have spurred the growth of EV-therapeutics, necessitating robust quality and safety assessments.
Purpose of the Study:
- To introduce physiologically based pharmacokinetic (PBPK) modeling as a key tool for predicting EV behavior in vivo.
- To provide a comprehensive overview of EV absorption, distribution, metabolism, and excretion (ADME) phenomena.
- To highlight the utility of PBPK modeling in optimizing EV-based drug delivery systems.
Main Methods:
- Application of PBPK modeling to predict EV pharmacokinetics.
- Gathering data on EV characteristics (size, shape, composition) and physiological factors.
- Utilizing PBPK models to simulate drug pharmacokinetics delivered by EVs.
Main Results:
- PBPK modeling enables prediction of EV absorption, distribution, metabolism, and excretion.
- Model outputs can guide the optimization of EV-drug formulations, including size, composition, administration route, and dosage.
- This review offers a dedicated overview of PBPK modeling for EVs, a topic previously lacking specific review articles.
Conclusions:
- PBPK modeling is a vital tool for advancing EV-therapeutics by predicting in vivo behavior and informing system design.
- Optimized EV-based drug delivery systems, guided by PBPK predictions, can enhance therapeutic outcomes.
- This work provides a foundation for future research in computational modeling for EV-based therapies.
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