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Human organotypic colon in vitro microtissue: unveiling a new window into colonic drug disposition.
Eur J Pharm Sci
January 2025
Preclinical Sciences & Translational Safety, Janssen R&D, Turnhoutseweg 30, 2340, Beerse, Belgium. Electronic address:
The purpose of this study was to evaluate EpiColon, a novel human organotypic 3D colon microtissue prototype, developed to assess colonic drug disposition, with a particular focus on permeability ranking, and compare its performance to Caco-2 monolayers. EpiColon was characterized for barrier function using transepithelial electrical resistance (TEER), morphology via histology and immunohistochemistry, and functionality through drug transport studies measuring apparent permeability (P). Cutoff thresholds for the permeability of FITC-dextran 4 kDa (FD4), FITC-dextran 10 kDa (FD10S), and [C]mannitol were established to monitor microtissue integrity.
View Article and Find Full Text PDFWhole-Body Physiologically Based Pharmacokinetic Modeling of GalNAc-Conjugated siRNAs.
Pharmaceutics
January 2025
Department of Pharmaceutical Bioscience, Translational Drug Discovery and Development, Uppsala University, SE-75124 Uppsala, Sweden.
: N-acetyl-galactosamine small interfering RNAs (GalNAc-siRNA) are an emerging class of drugs due to their durable knockdown of disease-related proteins. Direct conjugation of GalNAc onto the siRNA enables targeted uptake into hepatocytes via GalNAc recognition of the Asialoglycoprotein Receptor (ASGPR). With a transient plasma exposure combined with a prolonged liver half-life, GalNAc-siRNA exhibits distinct disposition characteristics.
View Article and Find Full Text PDFEffects of a Footbathing Intervention on Physiological, Endocrine, and Psychological Status in Japanese University Students: A Randomized Controlled Trial.
Int J Environ Res Public Health
December 2024
Faculty of Letters, Arts and Sciences, Waseda University, Tokyo 162-8644, Japan.
The present pilot study examined effectiveness of a 2-week footbathing intervention on physiological, endocrine, and psychological status in healthy Japanese university students. A total of 51 participants were randomly assigned to a footbathing or normal bathing group. Participants in both groups provided daily free descriptions of their physical and mental states during the intervention period.
View Article and Find Full Text PDFThe Influence of Cell Isolation and Culturing on Natriuretic Peptide Receptors in Aortic Vascular Smooth Muscle Cells.
Cells
January 2025
Institute of Anatomy & Cell Biology, Faculty of Medicine, Justus-Liebig-University, Aulweg 123, 35392 Giessen, Germany.
Vascular smooth muscle cell (SMC) relaxation by guanylyl cyclases (GCs) and cGMP is mediated by NO and its receptor soluble GC (sGC) or natriuretic peptides (NPs) ANP/BNP and CNP with the receptors GC-A and GC-B, respectively. It is commonly accepted that cultured SMCs differ from those in intact vessels. Nevertheless, cell culture often remains the first step for signaling investigations and drug testing.
View Article and Find Full Text PDFMeta-Analysis of the Input and Disposition of Various Dosage Forms of Methylprednisolone in Healthy Subjects Utilizing a Physiologically Based Pharmacokinetic Model.
AAPS J
January 2025
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, 160 Hayes Rd, Buffalo, New York, 14214, USA.
The study quantitatively analyzes and compares the pharmacokinetics (PK) of methylprednisolone (MPL) in humans upon administration of various dosage forms. The PK parameters and profiles of MPL in healthy subjects were collected from 22 literature sources. A minimal physiologically based pharmacokinetic (mPBPK) model consisting of blood and two tissue (lumped liver and kidney, remainder) compartments with nonlinear tissue partitioning was applied to describe MPL disposition.
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