title: Uptake and Permeability Studies to Delineate the Role of Efflux Transporters.
abstract: Chemotherapy is one of the major therapeutic interventions in oncology. Despite numerous advances and intensive research, a large number of patients acquire multidrug resistance (MDR) and no longer respond to chemotherapy. Efflux transporters play a predominant role in mediating MDR. Cellular accumulation (uptake) and permeability studies serve as invaluable methods to detect drug efflux/transport mechanism. These methods are generally performed on transfected cells (e.g., MDCKII-MDR1, MDCKII-MRP2, and MDCKII-BCRP) or cells expressing high amount of intrinsic efflux transporters (Caco-2) utilizing specific inhibitors as positive controls. This chapter presents a method of performing uptake and permeability studies, including the preparation of various buffers required for the study.
authors.affiliation: Technical Services, Mylan Pharmaceuticals Inc, 781 Chestnut Ridge Road, Morgantown, WV, 26505, USA.
authors.forename: Ramya Krishna
authors.initials: RK
authors.lastname: Vadlapatla
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO, 64108-2718, USA.
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Pal
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO, 64108-2718, USA. mitraa@umkc.edu.
authors.forename: Ashim K
authors.initials: AK
authors.lastname: Mitra
mesh_terms: D001692:Biological Transport; D018938:Caco-2 Cells; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations
keywords: Bidirectional permeability; DPBS buffer; Efflux transporters; Stop and lysis solutions; TEER values; Transwells; Uptake