Characterization of the inhibition of breast cancer resistance protein-mediated efflux of mitoxantrone by pharmaceutical excipients

International Journal of Pharmaceutics
Tetsuo YamagataYuichi Sugiyama

Abstract

Previously we showed that some excipients can inhibit breast cancer resistance protein (BCRP/ABCG2) in vitro and in vivo. We then evaluated the reversibility and the mode of BCRP inhibition of excipients, such as Tween 20 and Pluronic P85, by the intracellular mitoxantrone uptake study. To evaluate the reversibility of BCRP inhibitory effects, BCRP expressing cells were preincubated with the excipients and the intracellular mitoxantrone uptake was determined after removing or not removing the excipients. To evaluate the mode of BCRP inhibitory effects, the intracellular mitoxantrone uptake at the different mitoxantrone concentrations in the medium with the excipients was determined. Both Tween 20 and Pluronic P85 increased the mitoxantrone uptake in BCRP expressing cells, but these effects were disappeared when the excipients were removed. Moreover, both excipients increased the uptake at low substrate concentrations. However, at high substrate concentrations, Tween 20 increased the uptake to less extent compared with low substrate concentrations, whereas there was no such effect of Pluronic P85. Taken together, Pluronic P85 and Tween 20 appear to inhibit BCRP-mediated efflux of mitoxantrone reversibly and the inhibition mode o...Continue Reading

References

Dec 13, 2005·Trends in Pharmacological Sciences·Antonius E van Herwaarden, Alfred H Schinkel
Mar 29, 2007·Molecular Pharmaceutics·Guoyu Pan, William F Elmquist
Apr 21, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tetsuo YamagataYuichi Sugiyama
Sep 29, 2007·Journal of Controlled Release : Official Journal of the Controlled Release Society·Tetsuo YamagataYuichi Sugiyama

❮ Previous
Next ❯

Citations

May 27, 2010·Pharmaceutical Research·Leslie TompkinsHongbing Wang
Apr 16, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Stephen Timothy BuckleyMartin Brandl
Jul 24, 2012·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Bitte Aspenström-FagerlundAnders W Glynn
Jan 31, 2017·International Journal of Pharmaceutics·Sirima SoodvilaiPraneet Opanasopit
Jun 28, 2016·Pharmaceutical Development and Technology·Walter Javier StarkloffNoelia L Gonzalez Vidal
Feb 7, 2013·Pharmacological Reviews·Hywel D WilliamsChristopher J H Porter
Nov 20, 2016·International Journal of Cancer. Journal International Du Cancer·Nourhan K MohamedMahmoud Elsabahy
Jan 29, 2020·Molecular Pharmaceutics·Ling ZouKathleen M Giacomini

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.