Elucidating the mechanism of cellular uptake and removal
Polymyxins are a last-line therapy to treat MDR Gram-negative bacterial infections.
Nephrotoxicity is the dose-limiting factor for polymyxins and recent studies demonstrated significant accumulation of polymyxins in renal tubular cells.
Uptake measurement was performed with varying concentrations of the compound (ranging from 10 n M to 500 μM) added to the uptake buffer containing 2.5 μM [ of each compound was calculated by non-linear regression using Graph Pad Prism 6.0 (Graph Pad, La Jolla, CA, USA).
Each experiment was conducted independently three times with three replicates for each condition.
which suggests that other mechanisms also play key roles in the reabsorption of polymyxin by renal tubular cells.
Background counts of vector-transfected cells were subtracted from all uptake data.