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There is a considerable need to rationalize the membrane permeability and mechanism of transport for potential nutraceuticals. The aim of this investigation was to develop a theoretical permeability equation, based on a reported descriptive absorption model, enabling calculation of the transcellular component of absorption across Caco-2 monolayers. Published data for Caco-2 permeability of 30 drugs transported by the transcellular route were correlated with the descriptors 1-octanol/water distribution coefficient (log D, pH 7.4) and size, based on molecular mass. Nonlinear regression analysis was used to derive a set of model parameters a', β', and b' with an integrated molecular mass function. The new theoretical transcellular permeability (TTP) model obtained a good fit of the published data (R² = 0.93) and predicted reasonably well (R² = 0.86) the experimental apparent permeability coefficient (P(app)) for nine non-training set compounds reportedly transported by the transcellular route. For the first time, the TTP model was used to predict the absorption characteristics of six phenolic acids, and this original investigation was supported by in vitro Caco-2 cell mechanistic studies, which suggested that deviation of the P(app) value from the predicted transcellular permeability (P(app)(trans)) may be attributed to involvement of active uptake, efflux transporters, or paracellular flux.
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http://dx.doi.org/10.1124/dmd.111.041665 | DOI Listing |
Wei Sheng Yan Jiu
November 2024
West China School of Public Health, Sichuan University, Chengdu 610041, China.
Objective: To explore the possible mechanism of absorption of iron oxide nanoparticles into the human body through the gastrointestinal tract.
Methods: This article used Caco-2 monolayer cells as a cell model, prepared characterized iron oxide nanoparticles(Fe_2O_3 NPs) as suspensions, and intervened in Caco-2 cells. CCK-8 method, transwell method, and atomic spectrophotometer method were used to explore the effect of Fe_2O_3 NPs on the activity of Caco-2 cells and the absorption and transport of them through the Caco-2 monolayer cell model.
Biomater Sci
December 2024
National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, 430074 Wuhan, P. R. China.
Oral protein drugs' delivery faces challenges due to multiple absorption barriers for macromolecules. Co-administration with permeation enhancers and encapsulation in nano-carriers are two promising strategies to enhance their oral absorption. Herein, the poly(lactic--glycolic acid) nanoparticles (PLGA NPs) are decorated with polyethylene glycol (PEG) and a traditional Chinese medicine-derived permeation enhancer borneol (BO) for oral insulin delivery.
View Article and Find Full Text PDFJ Control Release
December 2024
Department of Biomedicine, Health & Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University, Jeonnam 58554, Republic of Korea; College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 58554, Republic of Korea. Electronic address:
Type 2 diabetes is a chronic disease characterized by insulin resistance and often worsened by obesity. Effective management involves the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to assist with glycemic control and weight management. However, these drugs must be administered subcutaneously due to their low oral bioavailability.
View Article and Find Full Text PDFFood Chem
December 2024
College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China; Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan, Hubei 430070, PR China. Electronic address:
Improving sea buckthorn flavonoids (SF) stability and bioacccessibility is of more practical significance for evaluating the total bioacccessibility of such foods. Therefore, we prepared nanoparticles using zein and gum Arabic (GA) by anti-solvent precipitation to encapsulate SF. Nanoparticles were characterized and assessed for their effect on the stability, release, bioaccessibility, absorption, and antioxidant properties of SF in the in vitro digestion and cell line.
View Article and Find Full Text PDFJ Pharm Sci
December 2024
Research and Development, AbbVie Inc., 1 North Waukegan Road, North Chicago, Illinois, 60064, United States.
Biopharmaceutical companies generate a wealth of data, ranging from in silico physicochemical properties and machine learning models to both low and high-throughput in vitro assays and in vivo studies. To effectively harnesses this extensive data, we introduce a statistical methodology facilitated by Accuracy, Utility, and Rank Order Assessment (AURA), which combines basic statistical analyses with dynamic data visualizations to evaluate endpoint effectiveness in predicting intestinal absorption. We demonstrated that various physicochemical properties uniquely influence intestinal absorption on a project-specific basis, considering factors like intestinal efflux, passive permeability, and clearance.
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