Search results for "Permeability"
showing 10 items of 596 documents
X-ray computed tomography and numerical analysis of water-saturated porous materials
2012
A method for imaging a water-saturated porous material is developed in order to simulate a fluid flow through it using the Lattice Boltzmann method. The value of its flow permeability is compared to the value for the same sample when it is dry. An explanation for the difference in the experimental values of permeability for air and water is sought. A reference is given by experimental values from flow measurements that are interpreted according to Darcy's law of permeability.
Oral biopharmaceutics tools – Time for a new initiative – An introduction to the IMI project OrBiTo
2013
OrBiTo is a new European project within the IMI programme in the area of oral biopharmaceutics tools that includes world leading scientists from nine European universities, one regulatory agency, one non-profit research organization, four SMEs together with scientists from twelve pharmaceutical companies. The OrBiTo project will address key gaps in our knowledge of gastrointestinal (GI) drug absorption and deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery. This will be achieved through novel prospective investigations to define new methodologies as well as refinement of existing tools. Extensive validation of novel and existing biopharm…
IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 3: Identifying gaps in system parameters by analysin…
2016
Three Physiologically Based Pharmacokinetic software packages (GI-Sim, Simcyp® Simulator, and GastroPlus™) were evaluated as part of the Innovative Medicine Initiative Oral Biopharmaceutics Tools project (OrBiTo) during a blinded “bottom-up” anticipation of human pharmacokinetics. After data analysis of the predicted vs. measured pharmacokinetics parameters, it was found that oral bioavailability (Foral) was underpredicted for compounds with low permeability, suggesting improper estimates of intestinal surface area, colonic absorption and/or lack of intestinal transporter information. Foral was also underpredicted for acidic compounds, suggesting overestimation of impact of ionisation on pe…
Establishment of a pulmonary epithelial barrier on biodegradable poly-L-lactic-acid membranes
2019
Development of biocompatible and functional scaffolds for tissue engineering is a major challenge, especially for development of polarised epithelia that are critical structures in tissue homeostasis. Different in vitro models of the lung epithelial barrier have been characterized using non-degradable polyethylene terephthalate membranes which limits their uses for tissue engineering. Although poly-L-lactic acid (PLLA) membranes are biodegradable, those prepared via conventional Diffusion Induced Phase Separation (DIPS) lack open-porous geometry and show limited permeability compromising their use for epithelial barrier studies. Here we used PLLA membranes prepared via a modification of the…
Image-Guided Synthesis Reveals Potent Blood-Brain Barrier Permeable Histone Deacetylase Inhibitors
2014
Recent studies have revealed that several histone deacetylase (HDAC) inhibitors, which are used to study/treat brain diseases, show low blood-brain barrier (BBB) penetration. In addition to low HDAC potency and selectivity observed, poor brain penetrance may account for the high doses needed to achieve therapeutic efficacy. Here we report the development and evaluation of highly potent and blood-brain barrier permeable HDAC inhibitors for CNS applications based on an image-guided approach involving the parallel synthesis and radiolabeling of a series of compounds based on the benzamide HDAC inhibitor, MS-275 as a template. BBB penetration was optimized by rapid carbon-11 labeling and PET im…
Molecular Mechanisms of the Crosstalk Between Mitochondria and NADPH Oxidase Through Reactive Oxygen Species—Studies in White Blood Cells and in Anim…
2014
Aims: Oxidative stress is involved in the development of cardiovascular disease. There is a growing body of evidence for a crosstalk between different enzymatic sources of oxidative stress. With the present study, we sought to determine the underlying crosstalk mechanisms, the role of the mitochondrial permeability transition pore (mPTP), and its link to endothelial dysfunction. Results: NADPH oxidase (Nox) activation (oxidative burst and translocation of cytosolic Nox subunits) was observed in response to mitochondrial reactive oxygen species (mtROS) formation in human leukocytes. In vitro, mtROS-induced Nox activation was prevented by inhibitors of the mPTP, protein kinase C, tyrosine kin…
Nanoencapsulation in Lipid-Core Nanocapsules Controls Mometasone Furoate Skin Permeability Rate and Its Penetration to the Deeper Skin Layers
2013
<b><i>Aims:</i></b> The influence of nanoencapsulation of mometasone furoate (MF) in poly(ε-caprolactone) lipid-core nanocapsules (LNC) on its in vitro human skin permeation and penetration was evaluated. <b><i>Methods:</i></b> Semisolid formulations were prepared by increasing the viscosity of LNC using a carbomer (Carbopol® Ultrez at 0.5% w/v). Two complementary techniques (the static Franz diffusion cell model and the Saarbrücken penetration model) were used to evaluate skin permeation/penetration. <b><i>Results:</i></b> The drug release rate was decreased by nanoencapsulation. The skin permeability of MF was control…
Distinctive phytotoxic effects of Cd and Ni on membrane functionality.
2009
Metal ions essential for plant growth, such as Fe, Mn, Ni, Cu or Zn, are taken up by plants from the soil solution through metal transporters at the plasma membrane, mainly of the ZIP and Nramp families. These transport systems, however, can also give entry to other metals (Al, Cd, Hg, Pb). Non-nutritive elements, as well as the essential nutrients at higher than metabolic concentrations, can cause phytotoxicity. We have studied previously the effects of an essential (Ni) and a non essential (Cd) heavy metal on root cell plasma membranes, the first selective barrier encountered when entering the plant, using rice as model plant. Distinctive effects of Cd and Ni on membrane function (i.e., E…
Vascular endothelial growth factor-A and platelet-derived growth factor-B combination gene therapy prolongs angiogenic effects via recruitment of int…
2008
Vessel stabilization and the inhibition of side effects such as tissue edema are essential in angiogenic gene therapy. Thus, combination gene transfers stimulating both endothelial cell and pericyte proliferation have become of interest. However, there is currently little data to support combination gene transfer in large animal models. In this study, we evaluated the potential advantages of such a strategy by combining the transfer of adenoviral (Ad) vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF)-B into rabbit hindlimb skeletal muscle. AdLacZ alone or in combination with AdVEGF-A were used as controls. Contrast-enhanced ultrasound, modified Miles assa…
Adjoint-based inversion for porosity in shallow reservoirs using pseudo-transient solvers for non-linear hydro-mechanical processes
2020
Abstract Porous flow is of major importance in the shallow subsurface, since it directly impacts on reservoir-scale processes such as waste fluid sequestration or oil and gas exploration. Coupled and non-linear hydro-mechanical processes describe the motion of a low-viscous fluid interacting with a higher viscous porous rock matrix. This two-phase flow may trigger the initiation of solitary waves of porosity, further developing into vertical high-porosity pipes or chimneys. These preferred fluid escape features may lead to localised and fast vertical flow pathways potentially problematic in the case of for instance CO2 sequestration. Constraining the porosity and the non-linearly related pe…