Next Article in Journal
Innovating on Inhaled Bioequivalence: A Critical Analysis of the Current Limitations, Potential Solutions and Stakeholders of the Process
Next Article in Special Issue
Pharmaceutical Formulations with P-Glycoprotein Inhibitory Effect as Promising Approaches for Enhancing Oral Drug Absorption and Bioavailability
Previous Article in Journal
Liqui-Mass Technology as a Novel Tool to Produce Sustained Release Liqui-Tablet Made from Liqui-Pellets
Previous Article in Special Issue
Improved Hygroscopicity and Bioavailability of Solid Dispersion of Red Ginseng Extract with Silicon Dioxide
Article

Pharmacokinetic Comparison between Methotrexate-Loaded Nanoparticles and Nanoemulsions as Hard- and Soft-Type Nanoformulations: A Population Pharmacokinetic Modeling Approach

College of Pharmacy, Chonnam National University, Gwangju 61186, Korea
*
Author to whom correspondence should be addressed.
Both authors contributed equally to this work.
Academic Editors: Patrick J. Sinko and Kishor M. Wasan
Received: 31 May 2021 / Revised: 5 July 2021 / Accepted: 8 July 2021 / Published: 9 July 2021
The purpose of this study was to identify and explore the differences in pharmacokinetics between different nanoformulations. This was done by comparing the pharmacokinetics of methotrexate-loaded nanoparticles [poly(lactic-co-glycolic acid); size of 163.70 ± 10.25 nm] and nanoemulsions (olive oil and Labrasol; size of 173.77 ± 5.76 nm), which represent hard- and soft-type nanoformulations, respectively. In addition, the population pharmacokinetic modeling approach as a useful tool for the comparison of pharmacokinetics between nanoformulations was newly proposed through this study. Significant pharmacokinetic differences were identified between nanoformulations through the new population pharmacokinetic modeling approach. As a result, the formulation type was explored as a significant covariate. The clearance and bioavailability of methotrexate-loaded nanoemulsions tended to decrease by 99% and increase by 19%, respectively, compared to those of the nanoparticles. The exploration of significant pharmacokinetic differences between drug formulations and their correlations presented in this study provide new perspectives on the development of nanoformulations. View Full-Text
Keywords: methotrexate-loaded nanoparticles; methotrexate-loaded nanoemulsions; hard-type nanoformulation; soft-type nanoformulation; population pharmacokinetic modeling methotrexate-loaded nanoparticles; methotrexate-loaded nanoemulsions; hard-type nanoformulation; soft-type nanoformulation; population pharmacokinetic modeling
Show Figures

Graphical abstract

  • Supplementary File 1:

    ZIP-Document (ZIP, 404 KiB)

  • Externally hosted supplementary file 1
    Link: https://zenodo.org/
    Description: Figure S1. Mean plasma concentration-time profiles of methotrexate after oral (A) or intravenous (B) administration of methotrexate-loaded nanoparticles (-●-, 5 mg/kg as methotrexate) and metho-trexate-loaded nanoemulsions (-○-, 0.06 or 0.024 mg/kg as methotrexate) in rats. Vertical bars represent standard deviation of the mean (n = 5). * p < 0.05 compared with the oral administration of nanoparticle. ** p < 0.05 compared with the intravenous administration of nanoparticle; Figure S2. Visual predictive check of the final model for methotrexate-loaded nanoformulations (including nanoparticles and nanoemulsions). Observed concentrations are depicted by dots. Black dashed lines indicate the 95th, 50th, and 5th percentiles of predicted concentrations. Blue shaded regions (with black boundary lines) indicate 95% confidence intervals for the predicted 5th and 95th percentiles. Red shaded regions indicate 95% confidence intervals for the predicted 50th percentiles. Red lines indicate the 95th, 50th, and 5th per-centiles of observed concentrations.
MDPI and ACS Style

Jeong, S.-H.; Jang, J.-H.; Lee, Y.-B. Pharmacokinetic Comparison between Methotrexate-Loaded Nanoparticles and Nanoemulsions as Hard- and Soft-Type Nanoformulations: A Population Pharmacokinetic Modeling Approach. Pharmaceutics 2021, 13, 1050. https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13071050

AMA Style

Jeong S-H, Jang J-H, Lee Y-B. Pharmacokinetic Comparison between Methotrexate-Loaded Nanoparticles and Nanoemulsions as Hard- and Soft-Type Nanoformulations: A Population Pharmacokinetic Modeling Approach. Pharmaceutics. 2021; 13(7):1050. https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13071050

Chicago/Turabian Style

Jeong, Seung-Hyun, Ji-Hun Jang, and Yong-Bok Lee. 2021. "Pharmacokinetic Comparison between Methotrexate-Loaded Nanoparticles and Nanoemulsions as Hard- and Soft-Type Nanoformulations: A Population Pharmacokinetic Modeling Approach" Pharmaceutics 13, no. 7: 1050. https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13071050

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop