Investigation into modification of mass transfer kinetics by acrolein in a renal biochip

In this study we present a method for investigating the effect of acrolein, a nephrotoxic and urotoxic metabolite of the anticancerous prodrugs ifosfamide and cyclophosphamide, in a blood-renal barrier bio-chip. The real time monitoring of mass transfers of caffeine, vitamin B12 and albumin in the biochip was performed thanks to an in vitro dialysis method. The diffusion coefficients of the solutes and their dialysance from the apical to the basolateral compartments were found to be molecular weight and cell-membrane dependent, thus demonstrating the cell-barrier functionality. The toxicity induced by the acrolein led to modifications to mass transfer properties which appeared to be acrolein dose, time and solute molecular weight dependent. Solute mass transfer across the cell layer increased with acrolein concentrations. The sensitivity of this analysis method contributes to identify the mass transfer properties and to monitor the modification to the renal parameter when submitted to toxic cell compounds. The results provide the foundation for exploring kidney behavior in response to drugs thanks to a blood-tissue barrier model using a technique based on in vitro dialysis and real time analysis. (C) 2011 Elsevier Ltd. All rights reserved.