(208c) Subcutaneous Co-Culture Tissue-on-a-Chip for Injection Simulation (SubCuTIS): A Platform for Evaluating Mab Transport and Theory-Aided Prediction of Bioavailability

The delivery of biotherapeutics via subcutaneous injection, an important route of drug administration, depends on drug transport within the complex subcutaneous tissue microenvironment. However, the development of effective subcutaneous injection formulations is currently hindered by the lack of reliable in vivo and in vitro testing models. To address this issue, we present a new subcutaneous tissue-on-a-chip model, which mimics subcutaneous drug transport through a three-dimensional co-culture tissue architecture and allows for quantitative determination of relevant transport rate constants. Our model captures key physiological characteristics of subcutaneous tissues and can differentiate macromolecular transport of various molecules, matching existing in vivo data. Coupled with theoretical transport modeling, our chip can also reveal subtle differences in local absorption rates of subcutaneous therapeutics. Finally, we developed a mathematical framework to predict clinical bioavailability based on the local absorption rate constants obtained from our chip. This technology broadens the applicability of organs-on-chips as a standardized and easy-to-use device for analyzing the subcutaneous adsorption of therapeutics.