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

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.

Drug delivery to the brain via the nasal route of administration: exploration of key targets and major consideration factors

“…Consequently, the degree of clearance of nanoformulations by the immune system should be considered in nasal-brain drug delivery. For example, in nanoparticles and nanoemulsions of similar sizes (Jang et al 2019 , 2020 ), the in vivo clearance of nanoparticles was larger than that of nanoemulsions, and opsonization was proposed as one of the causes (Jeong et al 2021b ). In this regard, past reports (Owens III and Peppas, 2006 ; Wani et al 2020 ) have suggested that the surface strength of nanoparticles was relatively easier to opsonize in the body than materials with soft surfaces such as nanoemulsions, and as a result, nanoparticles could be extensively phagocytosed by the immune system.…”

Efficacy analysis of targeted nanodrug for non-small cell lung cancer therapy

“…Pharmacokinetics is an important factor that can influence drug efficacy. The pharmacokinetics of free drugs differ significantly from drugs encapsulated in NPs, which may be due to differences in distribution characteristics of nanomaterial in vivo ( Jeong et al, 2021 ). Many studies have confirmed that the bioavailability of nanodrugs is significantly improved than that of free drugs ( Patel et al, 2018 ; Jang et al, 2019 , 2020 ).…”

Quantitative assessment of the relevance of organic-anion-transporting-polypeptide 1B1 and 2B1 polymorphisms in fexofenadine pharmacokinetic variants via pharmacometrics

“…The population pharmacokinetic models of fexofenadine established considering OATP1B1 or 2B1 genetic polymorphisms were fully evaluated and validated visually or numerically using Phoenix NLME and R-software (R Foundation, Vienna, Austria). Evaluations of the model were performed using generally applied tools for population-scale drug quantification model validations [ [11] , [12] , [13] , [14] , [15] , [16] ]. Applied tools include GOF (including distribution of residuals), visual predictive check (VPC), bootstrapping, and normalized prediction distribution error (NPDE).…”

“…Population pharmacokinetic variability and modeling studies of drugs are very useful scientific approaches to finding effective dosage regimens based on quantitative predictions [ [11] , [12] , [13] ]. Consideration of efficacy and safety through identification of the pharmacokinetic diversity of fexofenadine among individuals will be a very important concern in clinical practice [ [14] , [15] , [16] ].…”