The Impact of Liposomal Formulations on the Release and Brain Delivery of Methotrexate: An In Vivo Microdialysis Study.
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Hu Y, Rip J, Gaillard PJ, de Lange ECM, Hammarlund-Udenaes M
J Pharm Sci 106 (9) 2606-2613 [2017-09-00; online 2017-03-18]
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 (K
PubMed 28322936
DOI 10.1016/j.xphs.2017.03.009
Crossref 10.1016/j.xphs.2017.03.009
pii: S0022-3549(17)30166-1