Multilayer Spheroids To Quantify Drug Uptake and Diffusion in 3D

Research Overview

Predicting drug toxicity and efficacy needs quantitative models of uptake and diffusion. This study reported a 3D multilayer spheroid model plus a new algorithm to quantify uptake and inward diffusion of fluorescent calcein through gap junction intercellular communication.

Spheroids from a variety of cell types accumulated calcein over time when incubated with calcein-AM, a substrate of the efflux transporter P-glycoprotein. Accumulation decreased in spheroids overexpressing P-glycoprotein and increased with the inhibitors verapamil, loperamide, and cyclosporin A, while inward diffusion was negligible in spheroids lacking gap junction communication — cleanly separating transporter activity from intercellular diffusion.