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• W2899304098 abstract "Despite the promising features of liposomes as brain drug delivery vehicles, it remains uncertain how they influence the brain uptake in vivo. In order to gain a better fundamental understanding of the interaction between liposomes and the blood–brain barrier (BBB), it is indispensable to test if liposomes affect drugs with different BBB transport properties (active influx or efflux) differently. The aim of this study was to quantitatively evaluate how PEGylated (PEG) liposomes influence brain delivery of diphenhydramine (DPH), a drug with active influx at the BBB, in rats. The brain uptake of DPH after 30 min intravenous infusion of free DPH, PEG liposomal DPH, or free DPH + empty PEG liposomes was compared by determining the unbound DPH concentrations in brain interstitial fluid and plasma with microdialysis. Regular blood samples were taken to measure total DPH concentrations in plasma. Free DPH was actively taken up into the brain time-dependently, with higher uptake at early time points followed by an unbound brain-to-plasma exposure ratio (Kp,uu) of 3.0. The encapsulation in PEG liposomes significantly decreased brain uptake of DPH, with a reduction of Kp,uu to 1.5 (p < 0.05). When empty PEG liposomes were coadministered with free drug, DPH brain uptake had a tendency to decrease (Kp,uu 2.3), and DPH was found to bind to the liposomes. This study showed that PEG liposomes decreased the brain delivery of DPH in a complex manner, contributing to the understanding of the intricate interactions between drug, liposomes, and the BBB." @default.
• W2899304098 created "2018-11-09" @default.
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• W2899304098 date "2018-10-30" @default.
• W2899304098 modified "2023-10-17" @default.
• W2899304098 title "In Vivo Quantitative Understanding of PEGylated Liposome’s Influence on Brain Delivery of Diphenhydramine" @default.
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• W2899304098 doi "https://doi.org/10.1021/acs.molpharmaceut.8b00611" @default.
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• W2899304098 hasPublicationYear "2018" @default.
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