Microphysiological Conditions Do Not Affect MDR1-Mediated Transport of Rhodamine 123 above an Artificial Proximal...

Area of Science:

• Biotechnology
• Pharmacology
• Physiology

Background:

• Animal testing for pharmaceuticals faces limitations in cost and predictive accuracy.
• Standard cell cultures fail to replicate in vivo physiological conditions.
• Microphysiological systems offer a promising alternative for more accurate drug testing.

Purpose of the Study:

• To investigate the influence of pressure and flow on substance transport mediated by multidrug resistance protein 1 (MDR1).
• To analyze the kinetics of MDR1-mediated and passive transport across an artificial tubular barrier.
• To develop and validate a kinetic model for drug transport in a microphysiological system.

Main Methods:

• Utilized a microphysiological system with an artificial cell-based tubular barrier.
• Employed a miniaturized fluorescence measurement device for continuous tracking of rhodamine 123 transport over 48 hours.
• Applied experimental results and curve fitting to determine transport kinetics and identify an appropriate kinetic model.

Main Results:

• Demonstrated that applied pressure and flow significantly affect both active and passive transport of rhodamine 123.
• Identified Hill kinetics (with n=2) as a more suitable model than Michaelis-Menten for MDR1-mediated transport.
• Obtained kinetic values (K, V, Papp) comparable to existing in vivo and in vitro studies.

Conclusions:

• The developed proximal tubule-on-a-chip model accurately reflects physiological transport dynamics.
• The findings provide a validated kinetic model for understanding MDR1-mediated drug transport.
• This microphysiological system is suitable for pharmaceutical substance testing and pharmacokinetic investigations of renal transporters like MDR1.