Profiling pharmacokinetic (PK) In A Microfluidic Platform.

Anticancer therapies are evaluated based on efficacy and adverse effects, both of which are influenced by ADME properties. Understanding and mimicking the pharmacokinetic (PK) profiles of anticancer drugs is crucial for drug approval and patient outcomes. This need drives efforts to replicate these profiles in silico, in vitro, or in animal models. However, animal models raise ethical concerns and pose challenges due to interspecies PK variability.

PK profiles of anticancer drugs are typically simulated in silico, assessed in vitro, and further evaluated in vivo before progressing to early clinical trials, where most failures occur.

To mitigate risks of failure and reduce animal use, we introduce an innovative in vitro approach designed to replicate diverse PK profiles and therapeutic schedules for anticancer treatments. Our method integrates data from in silico, in vitro, in vivo, and clinical trials. Using our automated liquid handling system, we can simulate a range of PK profiles for one or multiple drugs, following customized therapeutic schedules, in addition to the traditional bolus dose.

Our system utilizes a sequence of addition/removal steps to control drug concentrations corresponding to specific points on the PK curve, minimizing mechanical stress. Customizable treatment schedules, ranging from 7 to 21 days or more, are possible. Our platform accommodates monotherapies, combination therapies, and washout intervals, and offers timepoint sample collection for both dynamic and endpoint assays within a streamlined workflow.

In summary, our platform and protocol provide technical advantages by being pumpless, mixerless, autonomous, and modular. It can deliver therapies according to customized PK profiles and therapeutic schedules, including those involving washouts, and is effective for both monotherapies and combination therapies. Compared to animal models, this platform offers significant advantages, eliminating the high costs of combination therapies in animal studies and preserving the viability of control groups during long-term experiments.