Related Experiment Video
Updated: Mar 6, 2026

Comprehensive Evaluation of the Effectiveness and Safety of Placenta-Targeted Drug Delivery Using Three Complementary Methods
Published on: September 10, 2018
The Impact of Liposomal Formulations on the Release and Brain Delivery of Methotrexate: An In Vivo Microdialysis
Yang Hu1, Jaap Rip2, Pieter J Gaillard3
1Translational PKPD Research Group, Department of Pharmaceutical Biosciences, Associate Member of SciLife Lab, Uppsala University, Box 591, Uppsala 75124, Sweden.
Abstract:
The impact of liposomal formulations on the in vivo release and brain delivery of methotrexate (MTX) was quantitatively assessed in rats. Two PEGylated liposomal MTX formulations based on hydrogenated soy phosphatidylcholine (HSPC) or egg-yolk phosphatidylcholine (EYPC) were prepared. The drug release and uptake into the brain after intravenous administration of both formulations were compared with unformulated MTX by determining the released, unbound MTX in brain and plasma using microdialysis. Total MTX concentrations in plasma were determined using regular blood sampling. The administration of both high- and low-dose EYPC liposomes resulted in 10 times higher extent of MTX release in plasma compared to that obtained from HSPC liposomes (p < 0.05). MTX itself possessed limited brain uptake with steady-state unbound brain-to-plasma concentration ratio (Kp,uu) of 0.10 ± 0.06. Encapsulation in HSPC liposomes did not affect MTX brain uptake (Kp,uu 0.11 ± 0.05). In contrast, EYPC liposomes significantly improved MTX brain delivery with a 3-fold increase of Kp,uu (0.28 ± 0.14 and 0.32 ± 0.13 for high- and low-dose EYPC liposomal MTX, respectively, p < 0.05). These results provide unique quantitative evidence that liposomal formulations based on different phospholipids can result in very different brain delivery of MTX.
Related Concept Videos
Modified-Release Drug Delivery Systems: Bioavailability
Therapeutic Drug Monitoring: Affecting Factors
Modified-Release Drug Delivery Systems: Influencing Factors
Modified-Release Drug Delivery Systems: Site-Targeted
Factors Affecting Drug Distribution: Tissue Permeability
Small molecules with a molecular weight below 500 to 600 Daltons can easily pass through the capillary membrane, gaining access to different tissues. Larger...
Bioavailability Enhancement: Drug Permeability Enhancement

