Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and...

Area of Science:

• Pharmacology
• Biotechnology
• Computational Biology

Background:

• Traditional preclinical drug discovery models often lack predictive accuracy.
• Microphysiological Systems (MPS) offer a promising in vitro platform for drug testing.
• Integrating experimental and computational approaches is key to improving drug discovery paradigms.

Purpose of the Study:

• To develop and demonstrate a systems pharmacology approach for Microphysiological Systems (MPS) technology.
• To enhance the mechanistic detail in preclinical drug discovery models.
• To improve the translation of in vitro findings to in vivo outcomes.

Main Methods:

• Utilized a systems pharmacology framework for MPS development and application.
• Incorporated detailed mechanistic analysis beyond traditional pharmacokinetic/pharmacodynamic (PK/PD) models.
• Conducted case studies on a liver/immune MPS, including PK data analysis and inflammation response modeling.
• Performed theoretical investigation of a four-MPS interactome to explore drug absorption, distribution, metabolism, and excretion (ADME) principles.

Main Results:

• Demonstrated the application of the systems pharmacology approach through case studies on a single MPS.
• Showcased the utility of a multi-MPS interactome model for understanding complex pharmacological processes.
• Provided a quantitative framework for designing multi-MPS experiments and operations.

Conclusions:

• The described systems pharmacology approach significantly enhances the predictive power of MPS for drug discovery.
• Mechanistic insights derived from MPS can be effectively translated from in vitro to in vivo.
• This integrated paradigm represents a substantial advancement in preclinical drug development methodologies.