Huadong Sun1, Edwin Cy Chow, Shanjun Liu, Yimin Du, K Sandy Pang. 1. University of Toronto, Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, Toronto, M5S 3M2, Canada +1 416 978 6164 ; +1 416 978 8511 ; ks.pang@utoronto.ca.
Abstract
BACKGROUND: The Caco-2 monolayer has been used extensively for the high-throughput screening of drug permeability and identification of substrates, inhibitors, and inducers of intestinal transporters, especially P-glycoprotein (P-gp). Traditionally, the Caco-2 monolayer is viewed as a single barrier rather than a polarized cell monolayer consisting of metabolic enzymes that are sandwiched between two membrane barriers with distinctly different transporters. OBJECTIVE: This review addressed the usefulness and limitations of the Caco-2 cell monolayer in drug discovery and mechanistic studies. METHODS: This mini-review covered applications of the Caco-2 monolayer, clarified misconceptions, and critically addressed issues on data interpretation. CONCLUSION: The catenary model extends the usefulness of Caco-2 monolayer and provides proper mechanistic insight and data interpretation.
BACKGROUND: The Caco-2 monolayer has been used extensively for the high-throughput screening of drug permeability and identification of substrates, inhibitors, and inducers of intestinal transporters, especially P-glycoprotein (P-gp). Traditionally, the Caco-2 monolayer is viewed as a single barrier rather than a polarized cell monolayer consisting of metabolic enzymes that are sandwiched between two membrane barriers with distinctly different transporters. OBJECTIVE: This review addressed the usefulness and limitations of the Caco-2 cell monolayer in drug discovery and mechanistic studies. METHODS: This mini-review covered applications of the Caco-2 monolayer, clarified misconceptions, and critically addressed issues on data interpretation. CONCLUSION: The catenary model extends the usefulness of Caco-2 monolayer and provides proper mechanistic insight and data interpretation.
Authors: Dulan B Gunasekara; Jennifer Speer; Yuli Wang; Daniel L Nguyen; Mark I Reed; Nicole M Smiddy; Joel S Parker; John K Fallon; Philip C Smith; Christopher E Sims; Scott T Magness; Nancy L Allbritton Journal: Anal Chem Date: 2018-10-30 Impact factor: 6.986