Dr. James McKim of IONTOX LLC, ScitoVation (Formerly The Hamner Institute), and British American Tobacco, present “An In Vitro Evaluation of Nicotine Kinetics Utilizing a Human Airway Model (Mucilair™) Combined With an Integrated Multi-Organ Culture Plate” at the 51st Congress of the European Societies of Toxicology in Porto, Spain
Dr. James McKim of IONTOX, ScitoVation (Formerly The Hamner Institute) and British American Tobacco will be presenting their findings from their recent study, “An In Vitro Evaluation of Nicotine Kinetics Utilizing a Human Airway Model (Mucilair™) Combined With an Integrated Multi-Organ Culture Plate”, at the 51stCongress of the European Societies of Toxicology in Porto, Spain.
The framework set out in the report entitled “Toxicity Testing in the 21st Century” (2007) focused on the need for the development of alternative methods to animal testing. Emphasis was placed on the use of human cells combined with adverse outcome pathways for determining adverse effects. Predicting systemic toxicity from in vitro data requires a platform that incorporates multiple organs interconnected via a fluidics network, in such a way that pharmacokinetic data can be integrated into the responses observed. The aim of this study was to evaluate a new Dynamic Multi-Organ Plate (DMOP) that provides the ability to use human tissues or cells, which are in communication via fluidics and dialysis. A simple transwell-based, two organ compartment model containing a human airway model (MucilAirTM) was used to measure nicotine kinetics and biochemical effects. A standard 6-well plate was fitted with a fluidics/dialysis network. The dialysis membrane allows for exchange of test article and metabolites while maintaining each cell type under optimized media conditions. There is no net gain or loss of fluid. Nicotine (1000 µM) was added to the apical side of the MucilAir™ model. Nicotine in the basolateral chamber diffused into the fluidics system via dialysis and was carried to the delivery well. A static sample from the basolateral and delivery chambers was collected every hour for 6 hrs. Perfusate from the fluidics system was collected at integrated one hour time intervals for 6 hr at a flow rate of 1 µL/min. Nicotine was first detected in the basolateral chamber at 1 hr and reached a maximum concentration (3-4 µg/mL) by 5 hr. Nicotine was first detected in the delivery chamber at approximately 3 hr and increased linearly up to 0.3 µg/mL. Nicotine in the run through perfusate was also detected at 3 hr. When kinetic data is combined with biochemical changes in key biomarkers extrapolating from in vitro to in vivo becomes more accurate. These data demonstrate that a meso-scale multi-organ culture platform linked by fluidics/dialysis can provide a means of evaluating pharmacokinetic and pharmacodynamic parameters to study the movement of chemicals and their metabolites between organs in order to extrapolate in vitro toxicity to in vivo systemic effects.