Physiologically Based Pharmacokinetic Modeling of Nanoparticles

Nanoparticles are frequently designed to improve the pharmacokinetics profiles and tissue distribution of small molecules to prolong their systemic circulation, target specific tissue, or widen the therapeutic window. The multifunctionality of nanoparticles is frequently presented as an advantage bu...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2019-01, Vol.108 (1), p.58-72
Main Authors: Yuan, Dongfen, He, Hua, Wu, Yun, Fan, Jianghong, Cao, Yanguang
Format: Article
Language:English
Subjects:
Animals
efficacy
Humans
Models, Biological
mononuclear phagocytic system
nanoparticle disposition
Nanoparticles - metabolism
PBPK
Pharmacokinetics
tissue distribution
Tissue Distribution - physiology
toxicity
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Summary:Nanoparticles are frequently designed to improve the pharmacokinetics profiles and tissue distribution of small molecules to prolong their systemic circulation, target specific tissue, or widen the therapeutic window. The multifunctionality of nanoparticles is frequently presented as an advantage but also results in distinct and complicated in vivo disposition properties compared with a conventional formulation of the same molecules. Physiologically based pharmacokinetic (PBPK) modeling has been a useful tool in characterizing and predicting the systemic disposition, target exposure, and efficacy and toxicity of various types of drugs when coupled with pharmacodynamic modeling. Here we review the unique disposition characteristics of nanoparticles, assess how PBPK modeling takes into account the unique disposition properties of nanoparticles, and comment on the applications and challenges of PBPK modeling in characterizing and predicting the disposition and biological effects of nanoparticles.
ISSN:0022-3549
1520-6017
DOI:10.1016/j.xphs.2018.10.037