Physiologically Based Pharmacokinetic Modeling of Extracellular Vesicles

Simple Summary Extracellular vesicles (EVs) are cell-derived structures that play a vital role in intercellular communication and have potential as drug delivery platforms. Physiologically based pharmacokinetic (PBPK) modeling can be employed to predict the behavior of EVs in the body, including absorption, distribution, metabolism, and excretion. This information is crucial for assessing the quality, safety, and efficacy of EV-based therapeutics. By integrating data on EV characteristics and physiological processes, PBPK models can optimize drug delivery system design, such as EV size and composition, administration route, and drug dosage. Future research may benefit from computer-based modeling approaches in EV-based therapeutic development.Abstract Extracellular vesicles (EVs) are lipid membrane bound-cell-derived structures that are a key player in intercellular communication and facilitate numerous cellular functions such as tumor growth, metastasis, immunosuppression, and angiogenesis. They can be used as a drug delivery platform because they can protect drugs from degradation and target specific cells or tissues. With the advancement in the technologies and methods in EV research, EV-therapeutics are one of the fast-growing domains in the human health sector. Therapeutic translation of EVs in clinics requires assessing the quality, safety, and efficacy of the EVs, in which pharmacokinetics is very crucial. We report here the application of physiologically based pharmacokinetic (PBPK) modeling as a principal tool for the prediction of absorption, distribution, metabolism, and excretion of EVs. To create a PBPK model of EVs, researchers would need to gather data on the size, shape, and composition of the EVs, as well as the physiological processes that affect their behavior in the body. The PBPK model would then be used to predict the pharmacokinetics of drugs delivered via EVs, such as the rate at which the drug is absorbed and distributed throughout the body, the rate at which it is metabolized and eliminated, and the maximum concentration of the drug in the body. This information can be used to optimize the design of EV-based drug delivery systems, including the size and composition of the EVs, the route of administration, and the dose of the drug. There has not been any dedicated review article that describes the PBPK modeling of EV. This review provides an overview of the absorption, distribution, metabolism, and excretion (ADME) phenomena of EVs. In addition, we will briefly describe the different computer-based modeling approaches that may help in the future of EV-based therapeutic research.

Automated summary

Extracellular vesicles (EVs) are cell-derived structures that play an important role in intercellular communication and drug delivery. Physiologically based pharmacokinetic (PBPK) modeling can predict the behavior of EVs in the body and optimize drug delivery system design.