Oral administration of hydrophobic and poorly intestinal epithelium-permeable drugs is a significant challenge. Herein, we report a new strategy to overcome this problem by using novel, pH-responsive, and membrane-active nanogels as drug carriers. Prepared by simple physical cross-linking of amphiphilic pseudopeptidic polymers with pH-controlled membrane-activity, the size and hydrophobicity-hydrophilicity balance of the nanogels could be well-tuned. Furthermore, the amphiphilic nanogels could release hydrophobic payloads and destabilize cell membranes at duodenum and jejunum pH 5.0-6.0, which suggests their great potential for intestinal drug delivery.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1021/acsami.8b15661 | DOI Listing |
BMC Vet Res
January 2025
College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, Henan, China.
Background: Coccidia are among the primary pathogens causing diarrhea and even fatalities in lambs. With the increasing use of chemical drugs to treat coccidiosis, the problem of drug resistance is becoming more and more threatening. Therefore, there is an urgent need to identify novel alternative drugs for the treatment of the lamb coccidia.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Clinical and Molecular Medicine (IKOM), Faculty of Medicine and Health Sciences, NTNU - Norwegian University of Science and Technology, Prinsesse Kristinas gt. 1, Trondheim, 7030, Norway.
Restoration of the intestinal epithelial barrier is crucial for achieving mucosal healing, the therapeutic goal for inflammatory bowel disease (IBD). During homeostasis, epithelial renewal is maintained by crypt stem cells and progenitors that cease to divide as they differentiate into mature colonocytes. Inflammation is a major effector of mucosal damage in IBD and has been found to affect epithelial stemness, regeneration and cellular functions.
View Article and Find Full Text PDFDrug Metab Dispos
January 2025
Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, Research Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical Sciences, China Pharmaceutical University, Nanjing, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China. Electronic address:
Silybin, a milk thistle extract, is a flavonolignan compound with hepatoprotective effect. It is commonly used in dietary supplements, functional foods, and nutraceuticals. However, the metabolism of silybin has not been systematically characterized in organisms to date.
View Article and Find Full Text PDFDrug Metab Dispos
January 2025
Department of Pharmaceutics, University of Washington, Seattle, Washington. Electronic address:
Physiologically based pharmacokinetic (PBPK) modeling is a physiologically relevant approach that integrates drug-specific and system parameters to generate pharmacokinetic predictions for target populations. It has gained immense popularity for drug-drug interaction, organ impairment, and special population studies over the past 2 decades. However, an application of PBPK modeling with great potential remains rather overlooked-prediction of diarrheal disease impact on oral drug pharmacokinetics.
View Article and Find Full Text PDFDrug Metab Dispos
January 2025
Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington. Electronic address:
To further the development of an in vitro model that faithfully recapitulates drug disposition of orally administered drugs, we investigated the utility of human enteroid monolayers to simultaneously assess intestinal drug absorption and first-pass metabolism processes. We cultured human enteroid monolayers from 3 donors, derived via biopsies containing duodenal stem cells that were propagated and then differentiated atop permeable Transwell inserts, and confirmed transformation into a largely enterocyte population via RNA sequencing analysis and immunocytochemistry (ICC) assays. Proper cell morphology was assessed and confirmed via bright field microscopy and ICC imaging of tight junction proteins and other apically and basolaterally localized proteins.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!