Regional difference in intestinal drug absorption as a measure for the potential effect of P-glycoprotein efflux transporters

Objective: The aim of the present study was to determine whether curcumin (CM) can prevent drug sensitivity of breast cancer (BC) cells when E andβ-E2 are administered together and whether the underlying mechanism involves modulation of drug efflux transporters.Methods: MCF7 BC cells were treated with the vehicle only, E+β-E2, or E+β-E2+CM repeatedly for 8 weeks. Afterward, the cells were harvested,counted, and isolated for total RNA extraction. Total RNA was then processed into cDNA and further processed for the determination of mRNAexpression patterns of drug efflux transporters (P-glycoprotein, BCRP, and MRP1).Results: Decreased sensitivity of BC cells was shown by the increased cell viability of MCF7 cells after 8 weeks. This condition was accompanied withincreased mRNA expression of P-glycoprotein, BCRP, and MRP1 in cells treated with E+β-E2, as compared with the vehicle only. CM, administered incombination with E+β-E2, resulted in decreased cell viability versus E and β-E2 and also decreased in mRNA expression of P-glycoprotein, BCRP, andMRP1.Conclusion: CM partially reversed the sensitivity loss of BC cells to E in the presence of β-E2 by modulating drug efflux transporters.

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Regional Intestinal Drug Absorption: Biopharmaceutics and Drug Formulation

Pharmaceutics ◽

10.3390/pharmaceutics13020272 ◽

2021 ◽

Vol 13 (2) ◽

pp. 272

Author(s):

Arik Dahan ◽

Isabel González-Álvarez

Keyword(s):

Drug Absorption ◽

Unmet Needs ◽

Drug Formulation ◽

Fluid Composition ◽

Mucosal Cell ◽

Special Issue ◽

Junction Resistance ◽

Intestinal Drug Absorption ◽

Carrier Mediated Transport ◽

Mechanistic Basis

The gastrointestinal tract (GIT) can be broadly divided into several regions: the stomach, the small intestine (which is subdivided to duodenum, jejunum, and ileum), and the colon. The conditions and environment in each of these segments, and even within the segment, are dependent on many factors, e.g., the surrounding pH, fluid composition, transporters expression, metabolic enzymes activity, tight junction resistance, different morphology along the GIT, variable intestinal mucosal cell differentiation, changes in drug concentration (in cases of carrier-mediated transport), thickness and types of mucus, and resident microflora. Each of these variables, alone or in combination with others, can fundamentally alter the solubility/dissolution, the intestinal permeability, and the overall absorption of various drugs. This is the underlying mechanistic basis of regional-dependent intestinal drug absorption, which has led to many attempts to deliver drugs to specific regions throughout the GIT, aiming to optimize drug absorption, bioavailability, pharmacokinetics, and/or pharmacodynamics. In this Editorial we provide an overview of the Special Issue "Regional Intestinal Drug Absorption: Biopharmaceutics and Drug Formulation". The objective of this Special Issue is to highlight the current progress and to provide an overview of the latest developments in the field of regional-dependent intestinal drug absorption and delivery, as well as pointing out the unmet needs of the field.

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Expression and Function of Organic Anion Transporting Polypeptides in the Human Brain: Physiological and Pharmacological Implications

Pharmaceutics ◽

10.3390/pharmaceutics13060834 ◽

2021 ◽

Vol 13 (6) ◽

pp. 834

Author(s):

Anima M. Schäfer ◽

Henriette E. Meyer zu Schwabedissen ◽

Markus Grube

Keyword(s):

Organic Anion ◽

Physiological Role ◽

Point Of View ◽

Efflux Transporters ◽

Organic Anion Transporting Polypeptides ◽

Current State ◽

P Glycoprotein ◽

The Central Nervous System ◽

And Function ◽

Uptake Transporters

The central nervous system (CNS) is an important pharmacological target, but it is very effectively protected by the blood–brain barrier (BBB), thereby impairing the efficacy of many potential active compounds as they are unable to cross this barrier. Among others, membranous efflux transporters like P-Glycoprotein are involved in the integrity of this barrier. In addition to these, however, uptake transporters have also been found to selectively uptake certain compounds into the CNS. These transporters are localized in the BBB as well as in neurons or in the choroid plexus. Among them, from a pharmacological point of view, representatives of the organic anion transporting polypeptides (OATPs) are of particular interest, as they mediate the cellular entry of a variety of different pharmaceutical compounds. Thus, OATPs in the BBB potentially offer the possibility of CNS targeting approaches. For these purposes, a profound understanding of the expression and localization of these transporters is crucial. This review therefore summarizes the current state of knowledge of the expression and localization of OATPs in the CNS, gives an overview of their possible physiological role, and outlines their possible pharmacological relevance using selected examples.

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PL1 Prediction of intestinal drug absorption in cell cultures: Caco-2 and beyond

European Journal of Pharmaceutical Sciences ◽

10.1016/s0928-0987(97)83978-4 ◽

1997 ◽

Vol 5 ◽

pp. S2

Keyword(s):

Cell Cultures ◽

Drug Absorption ◽

Intestinal Drug Absorption

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The Potential of Non-Ionic Surfactant Against P-Glycoprotein Efflux Transporters for Drug Development System

Journal of Bioequivalence & Bioavailability ◽

10.4172/jbb.1000357 ◽

2017 ◽

Vol 09 (06) ◽

Author(s):

Kulsirirat T ◽

Rukthong P ◽

Dechwongya P ◽

Sathirakul K

Keyword(s):

Drug Development ◽

Efflux Transporters ◽

Ionic Surfactant ◽

Development System ◽

P Glycoprotein

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Extract from Dioscorea bulbifera L. rhizomes aggravate pirarubicin-induced cardiotoxicity by inhibiting the expression of P-glycoprotein and multidrug resistance-associated protein 2 in the mouse liver

Scientific Reports ◽

10.1038/s41598-021-99264-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Li-rui Sun ◽

Qiu-shi Guo ◽

Wei Zhou ◽

Min Li

Keyword(s):

Multidrug Resistance ◽

Mouse Liver ◽

Adverse Reactions ◽

Heart Tissue ◽

Efflux Transporters ◽

Glycoprotein P ◽

Chinese Herbal ◽

Good Safety Profile ◽

P Glycoprotein ◽

Dioscorea Bulbifera

AbstractChinese herbal medicine is widely used because it has a good safety profile and few side effects. However, the risk of adverse drug reactions caused by herb-drug interactions (HDIs) is often overlooked. Therefore, the task of identifying possible HDIs and elucidating their mechanisms is of great significance for the prevention and treatment of HDI-related adverse reactions. Since extract from Dioscorea bulbifera L. rhizomes (DB) can cause various degrees of liver damage, it is speculated that HDIs may occur between DB extract and chemicals metabolized or excreted by the liver. Our study revealed that the cardiotoxicity of pirarubicin (THP) was increased by co-administration of DB, and the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2) in the liver was inhibited by DB extract, which led to the accumulation of THP in heart tissue. In conclusion, there are risks of the co-administration of DB extract and THP. The mechanism of HDIs can be better revealed by targeting the efflux transporters.

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