Objectives: The purpose of this study was to analyse P-glycoprotein (P-gp) expression in different human in-vitro cornea models (HCE-T epithelial model and Hemicornea construct) after stimulation with P-gp substrates (rhodamine 123, levofloxacin and acebutolol).
Methods: The influence of P-gp substrates on mRNA expression was analysed using reverse transcriptase polymerase chain reaction (PCR) and real-time PCR. The effect of stimulation on the transporter functionality was estimated with a digoxin efflux assay. The Caco-2 cell line was used as positive control.
Key Findings: The reverse transcriptase PCR results showed an increase in band intensity compared with the control medium for all substrates. The real-time PCR for the Caco-2 and HCE-T epithelial model yielded a similar outcome, in which all tested substrates upregulated P-gp. In contrast, the Hemicornea construct showed no significant increase in the mRNA expression after stimulation. Both in-vitro models possessed similar drug transport profiles after stimulation. A significantly increased efflux of digoxin was measured after 24 and 72 h of stimulation with levofloxacin and acebutolol.
Conclusions: The expression and functionality of the P-gp in corneal tissue can be influenced through time exposure with specific substrates. However, the exact mechanism still requires further elucidation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/jphp.12357 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Accelerated Endosomal Escape of Splice-Switching Oligonucleotides Enables Efficient Hepatic Splice Correction.
ACS Appl Mater Interfaces
January 2025
Faculty of Life Sciences, Department of Pharmaceutical Sciences, Laboratory of Macromolecular Cancer Therapeutics (MMCT), University of Vienna, Josef-Holaubek-Platz 2, 1090 Vienna, Austria.
Splice-switching oligonucleotides (SSOs) can restore protein functionality in pathologies and are promising tools for manipulating the RNA-splicing machinery. Delivery vectors can considerably improve SSO functionality in vivo and allow dose reduction, thereby addressing the challenges of RNA-targeted therapeutics. Here, we report a biocompatible SSO nanocarrier, based on redox-responsive disulfide cross-linked low-molecular-weight linear polyethylenimine (cLPEI), for overcoming multiple biological barriers from subcellular compartments to en-route serum stability and finally in vivo delivery challenges.
View Article and Find Full Text PDFModeling Heart Failure With Preserved Ejection Fraction Using Human Induced Pluripotent Stem Cell-Derived Cardiac Organoids.
Circ Heart Fail
January 2025
Bruce Rapport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel (I.R.H., N.K., C.B., O.C.).
Background: The therapeutic armamentarium for heart failure with preserved ejection fraction (HFpEF) remains notably constrained. A factor contributing to this problem could be the scarcity of in vitro models for HFpEF, which hinders progress in developing new therapeutic strategies. Here, we aimed at developing a novel, comorbidity-inspired, human, in vitro model for HFpEF.
View Article and Find Full Text PDFAdvancing diagnostics and disease modeling: current concepts in biofabrication of soft microfluidic systems.
In Vitro Model
June 2024
3B's Research Group, European Institute of Excellence in Tissue Engineering and Regenerative Medicine Headquarters, Parque de Ciência e Tecnologia, I3Bs - Research Institute on Biomaterials, Biodegradable and Biomimetics - University of Minho, Zona Industrial da Gandra - Avepark, Barco, Guimaraes, 4805-017 Portugal.
Soft microfluidic systems play a pivotal role in personalized medicine, particularly in in vitro diagnostics tools and disease modeling. These systems offer unprecedented precision and versatility, enabling the creation of intricate three-dimensional (3D) tissue models that can closely emulate both physiological and pathophysiological conditions. By leveraging innovative biomaterials and bioinks, soft microfluidic systems can circumvent the current limitations involving the use of polydimethylsiloxane (PDMS), thus facilitating the development of customizable systems capable of sustaining the functions of encapsulated cells and mimicking complex biological microenvironments.
View Article and Find Full Text PDFEndothelial and smooth muscle cell interaction with hydrothermally treated titanium surfaces.
In Vitro Model
June 2024
Department of Mechanical Engineering, Colorado State University, Fort Collins, CO USA.
Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, and the most common form is coronary artery disease (CAD). Treatment options include coronary artery bypass surgery (CABG) or percutaneous heart intervention (PCI), but both have drawbacks. Bare metal stents (BMS) are commonly used to treat CAD; however, they lead to restenosis.
View Article and Find Full Text PDFDevelopment and characterisation of a novel complex triple cell culture model of the human alveolar epithelial barrier.
In Vitro Model
June 2024
In Vitro Toxicology Group, Faculty of Medicine, Health and Life Sciences, Swansea University Medical School, Swansea University, Sketty, Wales SA2 8PP UK.
Unlabelled: Owing to increased pressure from ethical groups and the public to avoid unnecessary animal testing, the need for new, responsive and biologically relevant in vitro models has surged. Models of the human alveolar epithelium are of particular interest since thorough investigations into air pollution and the effects of inhaled nanoparticles and e-cigarettes are needed. The lung is a crucial organ of interest due to potential exposures to endogenous material during occupational and ambient settings.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!