Compound Absorption in Polymer Devices Impairs the Translatability of Preclinical Safety Assessments.

ABSTRACT: Organotypic and microphysiological systems (MPS) that can emulate the molecular phenotype and function of human tissues, such as liver, are increasingly used in preclinical drug development. However, despite their improved predictivity, drug development success rates have remained low with most compounds failing in clinical phases despite promising preclinical data. Here, it is tested whether absorption of small molecules to polymers commonly used for MPS fabrication can impact preclinical pharmacological and toxicological assessments and contribute to the high clinical failure rates. To this end, identical devices are fabricated from eight different MPS polymers and absorption of prototypic compounds with different physicochemical properties are analyzed. It is found that overall absorpti

SUBMITTER: Kemas AM 

PROVIDER: S-EPMC11469150 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature