Transport of anthracyclines and mitoxantrone across membranes by a flip-flop mechanism

De novo Lipogenesis Protects Cancer Cells from Free Radicals and Chemotherapeutics by Promoting Membrane Lipid Saturation

“…The difference between the NBD fluorescence 2 seconds after the addition of doxorubicin and the NBD fluorescence 4 minutes later was used as the measurement for the relative flip-flop rate of doxorubicin (34). To measure doxorubicin accumulation, the cells were analyzed using a fluorescence microscope (515-nm long-pass emission filter) 30 minutes after addition of doxorubicin (10 μmol/L) or fluorimetrically (excitation, 490 nm; emission, 580 nm).…”

“…However, for certain exogenous compounds including commonly used chemotherapeutics, such as doxorubicin, passive flip-flop is a major mechanism of entry into the cells (34). Because treatment of cells with exogenous polyunsaturated fatty acids is known to promote the uptake of doxorubicin (45), we determined whether inhibition of fatty acid synthesis would promote membrane flip-flop and doxorubicin uptake.…”

“…After addition of doxorubicin, there was a rapid quenching of NBD fluorescence, which is caused by the association of doxorubicin with phospholipids in the outer leaflet. As doxorubicin translocates to the inner leaflet, further quenching of NBD is observed (34).…”

Gold nanostars for efficient in vitro and in vivo real-time SERS detection and drug delivery via plasmonic-tunable Raman/FTIR imaging

“…MTX is a hydrophobic drug, slightly soluble in water, but with a high solubility in lipids as previously demonstrated. 30 With a lipid/water partitioning coefficient of around 230,000, it is rational to undertake that MTX crosses the plasma membrane at a high rate. 31 The MTX is an anticancer drug with significant clinical activity.…”

Modeling Cardiac Uptake and Negative Inotropic Response of Verapamil in Rat Heart: Effect of Amiodarone

“…An increased cardiac accumulation of doxorubicin has been reported in mdr1a Pgp deficient mice (11). We have previously interpreted the substantial increase in myocardial uptake of the Pgp substrate idarubicin in the presence of verapamil or amiodarone in terms of an impairment of Pgpmediated influx hindrance (12); however, this hypothesis remains open to debate in view of alternative explanations in terms of physico-chemical properties of these drugs (13), including the membrane transport of idarubicin by a flip-flop mechanism (14). Since cardiac Pgp pumps may alter intracardiac concentrations and hence the efficacy and toxicity of cardioactive drugs, an understanding of their role in myocardial drug uptake merits further investigations (7).…”