Current Approaches and Techniques in Physiologically Based Pharmacokinetic (PBPK) Modelling of Nanomaterials

Utembe, Wells; Clewell, Harvey J.; Sanabria, Natasha; Doganis, Philip; Gulumian, Mary

doi:10.3390/nano10071267

Cited by 44 publications

(59 citation statements)

References 153 publications

(380 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…, physicochemical properties, permeability, protein binding, and metabolism by hepatic enzymes) enables building a PBPK model to predict in vivo performance of formulations in human . For detailed concept of PBPK, please refer to recent reviews 167 , 168 . Lastly, the in vitro model should be conducive to understanding the mechanisms of action of LBFs.…”

Section: Summary and Future Perspectivesmentioning

confidence: 99%

In vitro and in vivo correlation for lipid-based formulations: Current status and future perspectives

Huang

Qin

Chen

et al. 2021

Acta Pharmaceutica Sinica B

View full text Add to dashboard Cite

Lipid-based formulations (LBFs) have demonstrated a great potential in enhancing the oral absorption of poorly water-soluble drugs. However, construction of in vitro and in vivo correlations (IVIVCs) for LBFs is quite challenging, owing to a complex in vivo processing of these formulations. In this paper, we start with a brief introduction on the gastrointestinal digestion of lipid/LBFs and its relation to enhanced oral drug absorption; based on the concept of IVIVCs, the current status of in vitro models to establish IVIVCs for LBFs is reviewed, while future perspectives in this field are discussed. In vitro tests, which facilitate the understanding and prediction of the in vivo performance of solid dosage forms, frequently fail to mimic the in vivo processing of LBFs, leading to inconsistent results. In vitro digestion models, which more closely simulate gastrointestinal physiology, are a more promising option. Despite some successes in IVIVC modeling, the accuracy and consistency of these models are yet to be validated, particularly for human data. A reliable IVIVC model can not only reduce the risk, time, and cost of formulation development but can also contribute to the formulation design and optimization, thus promoting the clinical translation of LBFs.

show abstract

Section: Summary and Future Perspectivesmentioning

confidence: 99%

In vitro and in vivo correlation for lipid-based formulations: Current status and future perspectives

Huang

Qin

Chen

et al. 2021

Acta Pharmaceutica Sinica B

View full text Add to dashboard Cite

show abstract

“…Oral absorption is a complex process of several interdependent biological events. Physiologically based pharmacokinetic (PBPK) modeling integrates these simultaneous events and simulates ADME (absorption, distribution, metabolism, and elimination) to describe drug exposures in individual physiological compartments (Li et al, 2017; Utembe et al, 2020). Various biorelevant conditions have been shaped to build the IVIVC for orally administered NDDS (Table 4).…”

Section: Ivivc For Nddsmentioning

confidence: 99%

“…However, PBPK modeling of NDDS is very challenging due to complex in vivo transport mechanisms such as MPS uptake, EPR effect, lymphatic transport, and enzyme degradation (Li et al, 2017). Also, mechanistic modeling of NDDS flanked by organ-specific protein-coronas is still in its infancy (Utembe et al, 2020).…”

Section: Oral Route Of Administrationmentioning

confidence: 99%

In vitro dissolution considerations associated with nano drug delivery systems

Gupta

Chen

Xie

2021

WIREs Nanomed Nanobiotechnol

View full text Add to dashboard Cite

Nano drug delivery systems (NDDS) offer promising solution for the translation of future nanomedicines. As bioavailability and therapeutic outcomes can be improved by altering the drug release from these NDDS, it becomes essential to thoroughly understand their drug release kinetics. Moreover, U.S. Food and Drug Administration requires critical evaluation of potential safety, efficacy, and public health impacts of nanomaterials. Spiraling up market share of NDDS has also stimulated the pharmaceutical industry to develop their cost‐effective generic versions after the expiry of patent and associated exclusivity. However, unlike the conventional dosage forms, the in vivo disposition of NDDS is highly intricate and different from their in vitro behavior. Significant challenges exist in the establishment of in vitro–in vivo correlation (IVIVC) due to incomplete understanding of nanoparticles' in vivo biofate and its impact on in vitro experimental protocols. A rational design of dissolution may serve as quality and quantity control tool and help develop a meaningful IVIVC for favorable economic implications. Clinically relevant drug product specifications (critical quality attributes) can be identified by establishing a link between in vitro performance and in vivo exposure. In vitro dissolution may also play a pivotal role to understand the dissolution‐mediated clearance and safety of NDDS. Prevalent in vitro dissolution methods for NDDS and their limitations are discussed in this review, among which USP 4 is gaining more interest recently. Researchers are working diligently to develop biorelevant in vitro release assays to ensure optimal therapeutic performance of generic versions of these NDDS. This article focuses on these studies and presents important considerations for the future development of clinically relevant in vitro release methods. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine

show abstract

“…Among all of these, PBPK modelling and simulation have been selected for the current research, because it provides a more mechanistic approach for studying drug disposition in individual organs and tissues, and even allows the prediction of human pharmacokinetics from preclinical research. In fact, this tool has gained attention in drug research and development, for both conventional [4,5] and nanoparticle formulations [6,7].…”

Section: Introductionmentioning

confidence: 99%

Physiologically Based Pharmacokinetic (PBPK) Model of Gold Nanoparticle-Based Drug Delivery System for Stavudine Biodistribution

et al. 2022

View full text Add to dashboard Cite

Computational modelling has gained attention for evaluating nanoparticle-based drug delivery systems. Physiologically based pharmacokinetic (PBPK) modelling provides a mechanistic approach for evaluating drug biodistribution. The aim of this work is to develop a specific PBPK model to simulate stavudine biodistribution after the administration of a 40 nm gold nanoparticle-based drug delivery system in rats. The model parameters used have been obtained from literature, in vitro and in vivo studies, and computer optimization. Based on these, the PBPK model was built, and the compartments included were considered as permeability rate-limited tissues. In comparison with stavudine solution, a higher biodistribution of stavudine into HIV reservoirs and the modification of pharmacokinetic parameters such as the mean residence time (MRT) have been observed. These changes are particularly noteworthy in the liver, which presents a higher partition coefficient (from 0.27 to 0.55) and higher MRT (from 1.28 to 5.67 h). Simulated stavudine concentrations successfully describe these changes in the in vivo study results. The average fold error of predicted concentrations after the administration of stavudine-gold nanoparticles was within the 0.5–2-fold error in all of the tissues. Thus, this PBPK model approach may help with the pre-clinical extrapolation to other administration routes or the species of stavudine gold nanoparticles.

show abstract

Current Approaches and Techniques in Physiologically Based Pharmacokinetic (PBPK) Modelling of Nanomaterials

Cited by 44 publications

References 153 publications

In vitro and in vivo correlation for lipid-based formulations: Current status and future perspectives

In vitro and in vivo correlation for lipid-based formulations: Current status and future perspectives

In vitro dissolution considerations associated with nano drug delivery systems

Physiologically Based Pharmacokinetic (PBPK) Model of Gold Nanoparticle-Based Drug Delivery System for Stavudine Biodistribution

Contact Info

Product

Resources

About