Pharmacokinetic Comparison between Methotrexate-Loaded Nanoparticles and Nanoemulsions as Hard- and Soft-Type Nanoformulations: A Population Pharmacokinetic Modeling Approach
Seung-Hyun Jeong1, Ji-Hun Jang1, Yong-Bok Lee1
1College of Pharmacy, Chonnam National University, Gwangju 61186, Korea.
Abstract:
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.
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