Premium
Measurement of Rhodamine 123 in Three‐Dimensional Organoids: A Novel Model for P‐Glycoprotein Inhibitor Screening
Author(s) -
Zhang Yuanjin,
Zeng Zhiyang,
Zhao Junfang,
Li Dali,
Liu Mingyao,
Wang Xin
Publication year - 2016
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12596
Subject(s) - p glycoprotein , organoid , rhodamine 123 , efflux , chemistry , bioavailability , pharmacology , verapamil , transporter , microbiology and biotechnology , biology , biochemistry , multiple drug resistance , gene , antibiotics , organic chemistry , calcium
P‐glycoprotein (P‐gp), as the most important efflux transporter in intestines, plays the key role to determine the bioavailability of many drugs. The three‐dimensional (3D) organoid model is suitable to imitate small intestinal epithelium. In this study, a rapid, sensitive and efficient method to measure rhodamine 123 (Rh123, P‐gp substrate) in 3D organoids was developed to analyse P‐gp‐mediated drug transport. Ultrasonic cell disruptor was used to smash the organoid, and automatic microplate reader was used for detecting the concentration of Rh123 (λ ex /λ em = 485/520 nm). Moreover, verapamil, quinidine and mitotane were used to make validation about this newly developed approach. All three P‐gp inhibitors significantly inhibited the transport of Rh123 into 3D organoids. Therefore, the above‐mentioned method could serve as a new model for P‐gp inhibitor screening in a high‐throughput way.