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Journal of Chromatography. A Feb 2022The peak parking method was applied to evaluate the surface diffusivity D of polystyrenes dissolved in a THF/heptane mixture and transported through porous silica...
The peak parking method was applied to evaluate the surface diffusivity D of polystyrenes dissolved in a THF/heptane mixture and transported through porous silica materials with various morphologies. With this method, the overall effective diffusivity D is measured experimentally with coarse-grained models like Maxwell equation allowing one to infer the particle diffusivity D. Such particle diffusivity has two main contributions: in-pore diffusivity D and surface diffusivity D. The diffusion within the pores is determined experimentally using either non-adsorbing conditions or calculated from particle porosity, particle tortuosity, and hydrodynamic hindrance. The surface diffusion coefficient D is usually determined using models considering parallel diffusion in the pores and at the surface but this assumption is rather crude. In this paper, to address this problem, another approach is proposed using the Brownian motion of molecules in the pore space. These two approaches lead to similar equations relating the effective diffusion coefficient D, the in-pore diffusion D and surface diffusion D. The surface diffusion is analyzed as a function of the surface affinity of the probes considered here (polystyrenes of different molecular weights/lengths). Such surface affinity depends both on the probe chain length and surface chemistry of the host solid (the latter being characterized here through the silanol surface density). For short chain lengths, a non-monotonic change in the surface diffusion with affinity (i.e. retention factor) is observed in some cases. Yet, generally, as expected, surface diffusion decreases upon increasing the surface affinity. In contrast to short chain lengths, the longest chain lengths are less sensitive to the silanol surface density.
Topics: Diffusion; Molecular Weight; Polystyrenes; Porosity; Silicon Dioxide
PubMed: 35066296
DOI: 10.1016/j.chroma.2022.462823 -
Advanced Drug Delivery Reviews Mar 2019Mucus is a dynamic barrier which covers and protects the underlying mucosal epithelial membrane against bacteria and foreign particles. This protection mechanism extends... (Review)
Review
Mucus is a dynamic barrier which covers and protects the underlying mucosal epithelial membrane against bacteria and foreign particles. This protection mechanism extends to include therapeutic macromolecules and nanoparticles (NPs) through trapping of these particles. Mucus is not only a physical barrier that limiting particles movements based on their sizes but it selectively binds with particles through both hydrophilic and lipophilic interactions. Therefore, nano-carriers for mucosal delivery should be designed to eliminate entrapment by the mucus barrier. For this reason, different strategies have been approached for both solid nano-carriers and liquid core nano-carriers to synthesise muco-diffusive nano-carrier. Among these nano-strategies, Self-Emulsifying Drug Delivery System (SEDDS) was recognised as very promising nano-carrier for mucus delivery. The system was introduced to enhance the dissolution and bioavailability of orally administered insoluble drugs. SEDDS has shown high stability against intestinal enzymatic activity and more importantly, relatively rapid permeation characteristics across mucus barrier. The high diffusivity of SEDDS has been tested using various in vitro measurement techniques including both bulk and individual measurement of droplets diffusion within mucus. The selection and processing of an optimum in vitro technique is of great importance to avoid misinterpretation of the diffusivity of SEDDS through mucus barrier. In conclusion, SEDDS is a system with high capacity to diffuse through intestinal mucus even though this system has not been studied to the same extent as solid nano-carriers.
Topics: Animals; Diffusion; Drug Delivery Systems; Emulsions; Humans; Mucus; Nanotechnology; Permeability
PubMed: 30974131
DOI: 10.1016/j.addr.2019.04.001 -
Magnetic Resonance in Medicine Jan 2022Diffusion MRI provides a valuable tool for imaging tissue microstructure. However, due to the lack of related experimental methods and specially designed phantoms, no...
Assessment of the effects of mimicking tissue microstructural properties on apparent diffusion coefficient and apparent exchange rate in diffusion MRI via a series of specially designed phantoms.
PURPOSE
Diffusion MRI provides a valuable tool for imaging tissue microstructure. However, due to the lack of related experimental methods and specially designed phantoms, no experimental study has been conducted yet to quantitatively assess the effects of membrane permeability, intracellular volume fraction (IVF), and intracellular diffusivity on the apparent diffusion coefficient (ADC) obtained from diffusion weighted imaging (DWI), and the effects of membrane permeability on the apparent exchange rate (AXR) obtained from filter exchange imaging (FEXI).
METHODS
A series of phantoms with three adjustable parameters was designed to mimic tissue microstructural properties including membrane permeability, IVF, and intracellular diffusivity. Quantitative experiments were conducted to assess the effects of these properties on ADC and AXR. DWI scans were performed to obtain axial and radial ADC values. FEXI scans were performed to obtain AXR values.
RESULTS
Axial ADC values range from 1.148 μm /ms to 2.157 μm /ms, and radial ADC values range from 0.904 μm /ms to 2.067 μm /ms. Radial ADC decreased with a decrease in fiber permeability. Decreased axial and radial ADC values with increased intra-fiber volume fraction, and increased polyvinylpyrrolidone (PVP) concentration of the intra-fiber space were observed. AXR values range from 2.1 s to 4.9 s . AXR increases with fiber permeability.
CONCLUSION
The proposed phantoms can quantitatively evaluate the effects of mimicking tissue microstructural properties on ADC and AXR. This new phantom design provides a potential method for further understanding the biophysical mechanisms underlying the change in ADC and diffusion exchange.
Topics: Cell Membrane Permeability; Diffusion; Diffusion Magnetic Resonance Imaging; Phantoms, Imaging
PubMed: 34435698
DOI: 10.1002/mrm.28990 -
Journal of Biomechanical Engineering Jul 2023The cartilage endplates (CEPs) on the superior and inferior surfaces of the intervertebral disk (IVD), are the primary nutrient transport pathways between the disk and...
The cartilage endplates (CEPs) on the superior and inferior surfaces of the intervertebral disk (IVD), are the primary nutrient transport pathways between the disk and the vertebral body. Passive diffusion is responsible for transporting small nutrient and metabolite molecules through the avascular CEPs. The baseline solute diffusivities in healthy CEPs have been previously studied, however alterations in CEP diffusion associated with IVD degeneration remain unclear. This study aimed to quantitatively compare the solute diffusion in healthy and degenerated human CEPs using a fluorescence recovery after photobleaching (FRAP) approach. Seven healthy CEPs and 22 degenerated CEPs were collected from five fresh-frozen human cadaveric spines and 17 patients undergoing spine fusion surgery, respectively. The sodium fluorescein diffusivities in CEP radial and vertical directions were measured using the FRAP method. The CEP calcification level was evaluated by measuring the average X-ray attenuation. No difference was found in solute diffusivities between radial and axial directions in healthy and degenerated CEPs. Compared to healthy CEPs, the average solute diffusivity was 44% lower in degenerated CEPs (Healthy: 29.07 μm2/s (CI: 23.96-33.62 μm2/s); degenerated: 16.32 μm2/s (CI: 13.84-18.84 μm2/s), p < 0.001). The average solute diffusivity had an inverse relationship with the degree of CEP calcification as determined by the normalized X-ray attenuation values (ß = -22.19, R2 = 0.633; p < 0.001). This study suggests that solute diffusion through the disk and vertebral body interface is significantly hindered by CEP calcification, providing clues to help further understand the mechanism of IVD degeneration.
Topics: Humans; Cartilage; Intervertebral Disc; Intervertebral Disc Degeneration; Biological Transport; Diffusion; Calcinosis
PubMed: 36752723
DOI: 10.1115/1.4056871 -
Journal of Controlled Release :... Feb 2024Drug delivery systems which rely on diffusion for mass transport, such as hydrogels and nanoparticles, have enhanced drug targeting and extended delivery profiles to... (Review)
Review
Drug delivery systems which rely on diffusion for mass transport, such as hydrogels and nanoparticles, have enhanced drug targeting and extended delivery profiles to improve health outcomes for patients suffering from diseases including cancer and diabetes. However, diffusion-dependent systems often fail to provide >0.01-1% drug bioavailability when transporting macromolecules across poorly permeable physiological tissues such as the skin, solid tumors, the blood-brain barrier, and the gastrointestinal walls. Convection-enabling robotic ingestibles, wearables, and implantables physically interact with tissue walls to improve bioavailability in these settings by multiple orders of magnitude through convective mass transfer, the process of moving drug molecules via bulk fluid flow. In this Review, we compare diffusive and convective drug delivery systems, highlight engineering techniques that enhance the efficacy of convective devices, and provide examples of synergies between the two methods of drug transport.
Topics: Humans; Diffusion; Biological Transport; Drug Delivery Systems; Blood-Brain Barrier; Neoplasms
PubMed: 38190971
DOI: 10.1016/j.jconrel.2024.01.008 -
Magnetic Resonance in Medicine May 2020Diffusion times longer than 50 ms are typically probed with stimulated-echo sequences. Varying the diffusion time in stimulated-echo sequences affects the T weighting of...
PURPOSE
Diffusion times longer than 50 ms are typically probed with stimulated-echo sequences. Varying the diffusion time in stimulated-echo sequences affects the T weighting of subcompartments, complicating the analysis of diffusion time dependence. Although inversion recovery preparation could be used to change the T weighting, it cannot ensure equal T weighting at arbitrary mixing times. In this article, a sequence that ensures constant T weighting over a wide range of diffusion times is presented.
METHODS
The proposed sequence features 2 independent longitudinal storage periods: TM and TM . Diffusion encoding is performed during TM , effectively coupling the diffusion time and TM . Equal T weighting at arbitrary diffusion times is realized by keeping the total mixing time TM + TM constant. The sequence was compared with conventional stimulated-echo measurements of diffusion in a 2-compartment phantom consisting of distilled water and paraffinum perliquidum. Additionally, in vivo DTI of the brain was carried out for 8 healthy volunteers with diffusion times ranging from 50 to 500 ms.
RESULTS
Diffusion time dependence of the axial and radial diffusivity was detected in the brain. Both sequences resulted in almost identical diffusivities in white matter. In regions containing partial volumes of gray and white matter, a dependency on T weighting was observed.
CONCLUSION
In accordance with previous studies, little variance of T values appeared to be present in healthy white matter. However, this is likely different in diseased tissue. Here, the proposed sequence can be effective in differentiating between diffusion time dependence and T weighting effects.
Topics: Brain; Diffusion; Diffusion Magnetic Resonance Imaging; Humans; Theophylline; White Matter
PubMed: 31657868
DOI: 10.1002/mrm.28046 -
European Radiology Mar 2024Whether the alternation of the glymphatic system exists in neurodevelopmental disease still remains unclear. In this study, we investigated structural and functional...
OBJECTIVES
Whether the alternation of the glymphatic system exists in neurodevelopmental disease still remains unclear. In this study, we investigated structural and functional changes in the glymphatic system in the treatment-naïve attention-deficit/hyperactivity disorder (ADHD) children by quantitatively measuring the Virchow-Robin spaces (VRS) volume and diffusion tensor image-analysis along the perivascular space (DTI-ALPS).
METHODS
Forty-seven pediatric ADHD patients and 52 age- and gender-matched typically developing (TD) children were recruited in this prospective study. The VRS volume was calculated using a semi-automated approach in axial T2-weighted images. Diffusivities along the x-, y-, and z-axes in the projection, association, and subcortical neural fiber areas were measured. The ALPS index, a ratio that accentuated water diffusion along the perivascular space, was calculated. The Mann-Whitney U test was used to compare the quantitative parameters; Pearson's correlation was used to analyze the correlation with clinical symptoms.
RESULTS
The cerebral VRS volume (mean, 15.514 mL vs. 11.702 mL) and the VRS volume ratio in the ADHD group were larger than those in the TD group (all p < 0.001). The diffusivity along the x-axis in association fiber area and ALPS index were significantly smaller in the ADHD group vs. TD group (mean, 1.40 vs.1.59, p < 0.05 after false discovery rate adjustment). Besides, the ALPS index was related to inattention symptoms of ADHD (r = - 0.323, p < 0.05).
CONCLUSIONS
Our study suggests that the glymphatic system alternation may participate in the pathogenesis of ADHD, which may be a new research direction for exploring the mechanisms of psycho-behavioral developmental disorders. Moreover, the VRS volume and ALPS index could be used as the metrics for diagnosing ADHD.
CLINICAL RELEVANCE STATEMENT
Considering the potential relevance of the glymphatic system for exploring the mechanisms of attention deficit/hyperactivity, the Virchow-Robin spaces volume and the analysis along the perivascular space index could be used as additional metrics for diagnosing the disorder.
KEY POINTS
• Increased Virchow-Robin space volume and decreased analysis along the perivascular space index were found in the treatment-naïve attention-deficit/hyperactivity disorder children. • The results of this study indicate that the glymphatic system alternation may have a valuable role in the pathogenesis of attention-deficit/hyperactivity disorder. • The analysis along the perivascular space index is correlated with inattention symptoms of attention-deficit/hyperactivity disorder children.
Topics: Humans; Child; Attention Deficit Disorder with Hyperactivity; Prospective Studies; Benchmarking; Diffusion; Image Processing, Computer-Assisted
PubMed: 37673963
DOI: 10.1007/s00330-023-10220-2 -
Physical Review Letters Aug 2020Diffusion-mediated surface phenomena are crucial for human life and industry, with examples ranging from oxygen capture by lung alveolar surface to heterogeneous...
Diffusion-mediated surface phenomena are crucial for human life and industry, with examples ranging from oxygen capture by lung alveolar surface to heterogeneous catalysis, gene regulation, membrane permeation, and filtration processes. Their current description via diffusion equations with mixed boundary conditions is limited to simple surface reactions with infinite or constant reactivity. In this Letter, we propose a probabilistic approach based on the concept of boundary local time to investigate the intricate dynamics of diffusing particles near a reactive surface. Reformulating surface-particle interactions in terms of stopping conditions, we obtain in a unified way major diffusion-reaction characteristics such as the propagator, the survival probability, the first-passage time distribution, and the reaction rate. This general formalism allows us to describe new surface reaction mechanisms such as for instance surface reactivity depending on the number of encounters with the diffusing particle that can model the effects of catalyst fooling or membrane degradation. The disentanglement of the geometric structure of the medium from surface reactivity opens far-reaching perspectives for modeling, optimization, and control of diffusion-mediated surface phenomena.
Topics: Cell Membrane; DNA; Diffusion; Models, Biological; Models, Chemical; Proteins; Surface Properties; Thermodynamics
PubMed: 32857533
DOI: 10.1103/PhysRevLett.125.078102 -
Journal of Mathematical Biology May 2023The effects of habitat heterogeneity on a diffusing population are investigated here. We formulate a reaction-diffusion system of partial differential equations to...
The effects of habitat heterogeneity on a diffusing population are investigated here. We formulate a reaction-diffusion system of partial differential equations to analyze the effect of resource allocation in an ecosystem with resource having its own dynamics in space and time. We show a priori estimates to prove the existence of state solutions given a control. We formulate an optimal control problem of our ecosystem model such that the abundance of a single species is maximized while minimizing the cost of inflow resource allocation. In addition, we show the existence and uniqueness of the optimal control as well as the optimal control characterization. We also establish the existence of an optimal intermediate diffusion rate. Moreover, we illustrate several numerical simulations with Dirichlet and Neumann boundary conditions with the space domain in 1D and 2D.
Topics: Ecosystem; Population Dynamics; Models, Biological; Diffusion
PubMed: 37217639
DOI: 10.1007/s00285-023-01932-6 -
The Journal of Chemical Physics Aug 2022Real-time feedback-driven single-particle tracking is a technique that uses feedback control to enable single-molecule spectroscopy of freely diffusing particles in...
Real-time feedback-driven single-particle tracking is a technique that uses feedback control to enable single-molecule spectroscopy of freely diffusing particles in native or near-native environments. A number of different real-time feedback-driven single-particle tracking (RT-FD-SPT) approaches exist, and comparisons between methods based on experimental results are of limited use due to differences in samples and setups. In this study, we used statistical calculations and dynamical simulations to directly compare the performance of different methods. The methods considered were the orbital method, the knight's tour (grid scan) method, and MINFLUX, and we considered both fluorescence-based and interferometric scattering (iSCAT) approaches. There is a fundamental trade-off between precision and speed, with the knight's tour method being able to track the fastest diffusion but with low precision, and MINFLUX being the most precise but only tracking slow diffusion. To compare iSCAT and fluorescence, different biological samples were considered, including labeled and intrinsically fluorescent samples. The success of iSCAT as compared to fluorescence is strongly dependent on the particle size and the density and photophysical properties of the fluorescent particles. Using a wavelength for iSCAT that is negligibly absorbed by the tracked particle allows for an increased illumination intensity, which results in iSCAT providing better tracking for most samples. This work highlights the fundamental aspects of performance in RT-FD-SPT and should assist with the selection of an appropriate method for a particular application. The approach used can easily be extended to other RT-FD-SPT methods.
Topics: Diffusion; Feedback; Particle Size; Single Molecule Imaging
PubMed: 36050025
DOI: 10.1063/5.0096729