A Microfluidic Perfusion Platform for In Vitro Analysis of Drug Pharmacokinetic-Pharmacodynamic (PK-PD) Relationships

Controlled pharmacokinetic anti-cancer drug concentration profiles lead to growth inhibition of colorectal cancer cells in a microfluidic device

“…This is an emerging field in microfluidics. 14,15,[20][21][22][23] We contribute to this emerging field by offering an alternative technology to induce and validate dynamic dosing, test a drug used in the clinic, and translate clinical pharmacokinetics to technical requirements. We foresee use of this technology in the drug discovery process, for example in the lead optimization process where a handful of drugs are tested and optimized in in vitro and in vivo models.…”

“…14,15 While cancer drug testing has been performed extensively in microfluidic cell culture systems, [16][17][18][19] mimicking in vivo-like drug concentrations over time on-chip has up to recently been largely neglected in the oncology field, with recent notable exceptions. [20][21][22][23] Several current solutions rely on active perfusion of cell culture chambers with dynamic drug concentrations. 22,23 This perfusion results in shear stress, which increases with a higher concentration change rate.…”

“…[20][21][22][23] Several current solutions rely on active perfusion of cell culture chambers with dynamic drug concentrations. 22,23 This perfusion results in shear stress, which increases with a higher concentration change rate. Systems in which cells are cultured in a separate compartment to prevent direct exposure to fluid flows suffer from other drawbacks.…”

“…Two clinically approved drugs, doxorubicin and gemcitabine, were administered to breast cancer cell line cells at in vivo-like concentrations. 22 To prevent shear stress, as this is often absent in interstitial tumor tissue due to deficient lymphatic drainage and increased interstitial and oncotic pressure, 24 we developed and characterized a two layer chip with a membrane for dynamic drug concentrations. Dynamic drug concentrations are administered by pre-programmed syringe pumps.…”

Modeling Pharmacokinetic Profiles for Assessment of Anti-Cancer Drug on a Microfluidic System

“…Furthermore, various microfluidic systems have been developed to recreate physiological tissue organization or inter-tissue interactions, which have been proposed for the prediction of PKs [ 21 , 22 ]. Although a lot of progress has been made for drug testing using microfluidic systems [ 23 , 24 , 25 ], few attempts have been made to model concentration-time curve of drug, which is essential for PK profile drug testing [ 26 ].…”