Diffusion Relaxation Research Articles

Evaluation of Preclinical Efficacy of Curcumin-Loaded Bicosome Systems in Amelioration of Oral Mucositis

Background/Objectives: Oral mucositis (OM) is a common and debilitating side effect of cancer therapy, characterized by ulceration or inflammation of the oral mucosa. This study evaluates the preclinical efficacy of curcumin-loaded bicosome systems (cur-BS) in mitigating chemotherapy-induced OM in mice. Methods: BS were prepared using a combination of 1,2-di-palmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC), α-tocopherol, and curcumin, encapsulated within liposomal vesicles. Three formulations with different curcumin concentrations (180, 540, and 900 μM) were characterized by particle size, polydispersity index (PDI), encapsulation efficiency (EE), appearance, and morphology. The formulation with the highest concentration (cur-BS 5×) was selected for ex vivo permeability studies, release profile analysis, and in vitro anti-inflammatory efficacy. OM was induced in mice using 5-fluorouracil (5-FU) and acetic acid. Cur-BS 5× was compared to the commercial product Dentoxol®. Results: The results showed that cur-BS 5× provided sustained release through a mechanism involving both diffusion and matrix relaxation, enhancing curcumin retention in deeper skin layers. Treatment with cur-BS 5× downregulated the expression of inflammatory markers (IL-1β and TNF-α). Macroscopic assessments demonstrated that both cur-BS 5× and Dentoxol® reduced OM severity, with the greatest improvement observed between days 6 and 9. By day 24, OM scores were 1.25 ± 0.5 for cur-BS 5× and 1.0 ± 0.0 for Dentoxol®, indicating effectiveness in both treatments. However, histological analysis revealed superior tissue recovery with cur-BS 5×, showing better epithelial structure and reduced inflammation. Cur-BS 5×-treated mice also exhibited greater weight recovery and higher survival rates compared to the Dentoxol® group. Conclusions: These findings suggest that cur-BS 5× may enhance OM treatment, offering outcomes comparable to or better than those of Dentoxol®.

Synthesis of photo-responsive κ-carrageenan-based hydrogels for drug delivery application.

Natural polymer-based hydrogels may act as versatile platforms in controlled drug delivery. In this regard, photoactive κ-carrageenan (κ-Crg) hydrogels modified with cinnamate (CN) groups are developed for pH-sensitive release of drugs. κ-Crg-CN derivatives containing 17%, 33%, and 49% cinnamate contents, named κ-Crg-CN1, κ-Crg-CN2, and κ-Crg-CN3, respectively, are prepared and cross-linked by UV-induced [2π+2π] cycloaddition. Fourier transform infrared (FTIR) spectroscopy, Nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and elemental analysis are conducted for structural characterization. Rheological measurements showed an increased degree of cross-linking density with the increase in cinnamate content, as represented by storage modulus (G') values of 226Pa for κ-Crg-CN1, 631Pa for κ-Crg-CN2, and 967Pa for κ-Crg-CN3. Also, drug encapsulation efficiency using theophylline was significantly improved: 48% for κ-Crg-CN1, 63% for κ-Crg-CN2, and 85% for κ-Crg-CN3. Theophylline release studies showed that at pH1.2, it was slower than pH7.2, with a release rate inversely proportional to the cinnamate content. Kinetic modeling showed a non-Fickian transport mechanism that involved diffusion and polymer relaxation. These results show that κ-Crg-CN hydrogels can act as tunable, pH-sensitive drug delivery systems, with mechanical properties and release profiles precisely tailored by cinnamate functionalization for applications in controlled drug delivery.

Variability of multidimensional diffusion–relaxation MRI estimates in the human brain

Abstract Diffusion–relaxation correlation multidimensional MRI (MD-MRI) replaces voxel-averaged diffusion tensor quantities and R1 and R2 relaxation rates with their multidimensional distributions, enabling the selective extraction and mapping of specific diffusion–relaxation spectral ranges that correspond to different cellular features. This approach has the potential of achieving high sensitivity and specificity in detecting subtle changes that would otherwise be averaged out. Here, the whole brain characterization of MD-MRI distributions and derived parameters is presented and the intrascanner test–retest reliability, repeatability, and reproducibility are evaluated to promote the further development of these quantities as neuroimaging biomarkers. We compared white matter tracts and cortical and subcortical gray matter regions, revealing notable variations in their diffusion–relaxation profiles, indicative of unique microscopic morphological characteristics. We found that the reliability and repeatability of MD-MRI-derived diffusion and relaxation mean parameters were comparable with values expected in conventional diffusion tensor imaging and relaxometry studies. Importantly, the estimated signal fractions of intravoxel spectral components in the MD-MRI distribution, corresponding to white matter, gray matter, and cerebrospinal fluid, were found to be reproducible. This underscores the viability of employing a spectral analysis approach to MD-MRI data. Our results show that a clinically feasible MD-MRI protocol can reliably deliver information of the rich structural and chemical variety that exists within each imaging voxel, creating potential for new MRI biomarkers with enhanced sensitivity and specificity.

Hydrogen behavior and microstructural evolution in flexible IGZO thin films under stress

In this study, we investigated the effect of mechanical stress on hydrogen diffusion in flexible amorphous InGaZnO (a-IGZO) thin films and the resulting microstructural changes. The cyclic bending test under different curvature radii (R) revealed significant morphological evolution and bond state changes in IGZO thin films. As the curvature radius decreases from 20 mm to 5 mm, the surface of the sample gradually becomes rough and cracks appear. Simultaneously, changes in nanoscale topological structure and chemical composition exhibit stronger hydrogen diffusion and structural relaxation: The oxygen-hydrogen (O-H) bond content increased from 19 % to 55 %, while the metal-oxygen (M − O) bond content decreased from 50 % to 28 %. The M − H content increased, and In-H related structures underwent transformation. The radius of gyration (Rg) increasing from 1.652 nm to 1.812 nm. These results provide quantitative insights into the stability and performance of IGZO-based flexible electronic devices under mechanical deformation.

In vivo rat brain mapping of multiple gray matter water populations using nonparametric D(ω)-R1-R2 distributions MRI.

Massively multidimensional diffusion magnetic resonance imaging combines tensor-valued encoding, oscillating gradients, and diffusion-relaxation correlation to provide multicomponent subvoxel parameters depicting some tissue microstructural features. This method was successfully implemented ex vivo in microimaging systems and clinical conditions with tensor-valued gradient waveform of variable duration giving access to a narrow diffusion frequency (ω) range. We demonstrate here its preclinical in vivo implementation with a protocol of 389 contrast images probing a wide diffusion frequency range of 18 to 92 Hz at b-values up to 2.1ms/μm2 enabled by the use of modulated gradient waveforms and combined with multislice high-resolution and low-distortion echo planar imaging acquisition with segmented and full reversed phase-encode acquisition. This framework allows the identification of diffusion ω-dependence in the rat cerebellum and olfactory bulb gray matter (GM), and the parameter distributions are shown to resolve two water pools in the cerebellum GM with different diffusion coefficients, shapes, ω-dependence, relaxation rates, and spatial repartition whose attribution to specific microstructure could modify the current understanding of the origin of restriction in GM.

Transport Properties and Morphology of Cerium Oxide Composite Sulfonated(Poly Arylene Ether Sulfone) Membranes for Application in Heavy-Duty Fuel Cell Vehicles

Fuel cells for Heavy Duty Vehicles (HDVs) offer easy scalability and the potential for critical reduction in CO2 emissions. During the drive cycles of HDVs, the fuel cells will operate over a range of temperatures, with increases while climbing up steep gradients. Operating temperatures above 90°C will be necessary, along with low relative humidity (RH) due to the need to avoid pressurization of gases. Therefore, Proton Exchange Membranes (PEMs) for HDV applications need to be suitable over this range of conditions, including functioning at high temperatures and low relative humidity. Moreover, the membranes should not swell extensively when more water is present.In this study, sulfonated poly (arylene ether sulfone) multiblock copolymers were modified with the incorporation of clusters of modified cerium oxide nanoparticles to form composites. These synthesized novel membranes approach operational proton conductivity requirements for HDV vehicles, with conductivity of 15mS/cm at 120°C and 25% relative humidity, remarkably avoiding the typical large decrease in conductivity observed below 70% RH in non-fluorinated PEMs. One purpose of this study is to understand the water, proton, and polymer interactions within these membranes. The cerium nanoparticles and sulfonamide clusters play a critical role in the membrane, affecting conductivity, and water transport, especially at high temperatures and low relative humidity, while also suppressing swelling of the membrane. Membrane proton conductivity is also strongly influenced by physical properties such as water uptake and dimensional swelling behavior, which is further impacted by polymer morphology. To probe the dynamics of the components, the diffusion coefficient and relaxation time of water in the membrane and the protonic conductivity of the membrane as functions of membrane water content are analyzed using nuclear magnetic resonance (NMR) measurements and water uptake measurements. Film property and morphology changes are evaluated using Transmission Electron Microscopy (TEM) and Small-Angle X-ray Scattering (SAXS). This study demonstrates the advantageous and non-linear benefits of closely packed acid clusters with cerium oxide composites on membrane functionality under HDV operating conditions.

In vitro skin permeation of flavonoid esters enzymatically derived from natural oils: release mechanism from gel emulsion, stability, and dermatological compatibility

Due to their broad spectrum of biological activities and attractive pharmacological properties, flavonoids are very promising molecules for application in skin care products. In this study, phloridzin and naringin medium- and long-chain fatty acid esters were enzymatically synthesized in reaction with natural oils (coconut and linseed oil) and in vitro transdermal delivery of synthesized esters through artificial Strat-M® membrane was investigated. Experimental results were succesfully fitted using Peppas and Sahlin model which includes the lag phase. Release kinetics of all examined flavonoid esters from gel emulsions through the membrane depended on both diffusion and polymer relaxation effect (0.5<n < 1). The estimated effective diffusion coefficients ranged from 0.168·10-8 to 6.149·10-8 cm2 s-1 for phloridzin esters and from 0.116·10-8 to 4.210·10-8 cm2 s-1 for naringin esters. The effective diffusion coefficients decreased with the increase in ester molecular weight indicating the size-dependent diffusion. All formulation showed good stability, excellent hydration effect, and excellent dermatological compatibility without irritating effect. It can be concluded that gel emulsions with a mixture of flavonoid esters enzymatically synthesized in reaction with vegetable oils can be effectively topically applied as a skin care products.

Delivery system for dexamethasone phosphate based on a Zn2+-crosslinked polyelectrolyte complex of diethylaminoethyl chitosan and chondroitin sulfate

Hybrid nano- and microparticles based on metal ion crosslinked biopolymers are promising carriers for the development of drug delivery systems with improved biopharmaceutical properties. In this work, dexamethasone phosphate-containing particles based on chondroitin sulfate and chitosan or diethylaminoethyl chitosan additionally crosslinked with Zn2+ were prepared. Depending on the polycation/polyanion ratio in the system, anionic and cationic polyelectrolyte complexes (PECs) were obtained. The anionic Zn2+-containing and Zn2+-free PECs had sizes of 154 and 180 nm and ζ-potentials of −22.4 and −27.5 mV, respectively. The cationic Zn2+-containing and Zn2+-free PECs had sizes of 242 and 362 nm and ζ-potentials of 22.4 and 24.7 mV, respectively. The presence of Zn2+ in the system significantly prolonged the release of dexamethasone phosphate from the hybrid polyelectrolyte particle. The resulting release profiles of dexamethasone phosphate were in agreement with the Peppas-Sahlin kinetic model, which considers the combined effects of Fickian diffusion and polymer chain relaxation on the drug release rate. It was shown that the prolongation of drug release was mainly due to swelling and relaxation of the Zn2+ crosslinked polymers. The developed particles exhibited good mucoadhesive properties and pronounced anti-inflammatory activity, making them attractive candidates for biomedical applications.

Modeling Kinetics and Transport Mechanism Study of Poorly Soluble Drug Formulation in High Acidic Medium

Some medicinal particles are poorly soluble in highly acidic solutions, particularly those subjected to various production processes. Therefore, the present research investigated the kinetics and mechanisms of the drug release rate of newly formulated solid pills in a low pH medium. Three pills were prepared: one from a non-moisturized powder mixture (PILD) and the other two, PILC and PILM, from the dried powder mixtures, which were dried using hot-air heating and microwave radiation, respectively. These pills were subjected to drug release tests, and the outcomes were considered in the kinetics investigation using various models. Zero-order, Hixson–Crowell, First-order, Higuchi, Hopfenberg, Korsmeyer-Peppas, Logistic, and Peppas-Sahlin were the kinetic models used to inspect the release rate mechanism of these tablets. It was found that the Peppas-Sahlin and zero-order were the most reliable models to represent the drug release profile of all prepared pills with very high accuracy, estimated by R^2&gt;0.99. The Hixon and first-order models were the weakest to characterize this work outcome. This work also applied these models to describe the controlling mechanism of the drug release for each prepared pill. It is detected that the non-Fickian diffusion and polymer chain relaxation control the PILC’s release behavior. However, case II transport and super case II transport with erosions is the dominant mechanism for PILD and PILM pills, respectively. Additionally, new semi-empirical models were modified to describe the kinetics of the solid release of those tablets with greater accuracy.

On the kinetics of structural evolution in metallic glasses

The classic phenomenological models fail to describe the physical landscape of creep deformation for amorphous solids. In this paper, creep behavior of typical metallic glasses with chemical compositions La62Al14Ag2.34Ni10.83Co10.83, Pd20Pt20Cu20Ni20P20 and Cu46Zr39Hf8Al7 were studied. Instead, we attempt to use a modified hierarchically correlated model informed by physics to realize the creep behaviors of metallic glasses. The anelastic deformation of creep is categorized into two distinct components, i.e., the highly correlated deformation unit sensitive to annealing and the low correlated unit associated with diffusion relaxation. The correlated component diminishes with structural aging. The validity of the model is verified by these findings, and the derived parameters provide insights into the structural and kinetic characteristics of metallic glasses. Decreased characteristic times and contrasting correlation factors indicate homogeneous structure and lower energy states. Moreover, a qualitative evaluation of the relative strengths of the dual deformation mechanisms during creep enables the characterization of β relaxation forms, shedding light on the intrinsic attributes of different types of metallic glasses. This methodology additionally facilitates the detection of structural aging and rejuvenation phenomena.

Development of pH‐Sensitive Microbeads Incorporated with Amine‐Functionalized Magnetic Nanoparticles for Enhanced Antibacterial Activity

AbstractAntibiotic‐resistant bacteria have rapidly emerged in recent years as a result of irrational use of antibiotics. The development of drug carriers that can enhance antibacterial activity of antibiotics can potentially overcome antibiotic resistance and hence has practical significance. This study addresses this need by integrating amine‐functionalized magnetic nanoparticles (AMNPs) into hydrogel microbeads composed of sodium alginate (SA) and xanthan gum (XG) for delivery of levofloxacin (LVX). Characterization of the microbeads confirmed successful AMNP–polymer interactions and demonstrated a porous structure inside the microbeads. The microbeads demonstrated pH‐sensitive drug release behavior, enabling prolonged drug release. The drug encapsulation efficiency in the hydrogel microbeads was higher after AMNP incorporation, indicating the potential roles played by the porous network and by AMNP‐LVX interactions during drug loading. The microbeads adhered to first‐order, Higuchi, and Korsmeyer‐Peppas kinetic models, suggesting that a combination of diffusion and polymer relaxation mechanisms is involved in drug release. Along with the fact that the AMNP‐incorporated microbeads exhibited enhanced antibacterial activity against various bacterial strains, our microbeads warrant further development and optimization as drug carriers for antibacterial applications.

In vitro assessment of skin permeation properties of enzymatically derived oil-based fatty acid esters of vitamin C.

Current topical formulations containing vitamin C face limitations in therapeutic effectiveness due to the skin's selective properties that impede drug deposition. Consequently, the widespread use of toxic and irritating chemical permeation enhancers is common. Hereby, we investigated enzymatically derived fatty acid ascorbyl esters (FAAEs) obtained using natural oils for their skin permeation properties using the Strat-M® skin model in a Franz cell diffusion study. By evaluating various cosmetic formulations without added enhancers, we found that emulgel is most suitable for enhancing the cutaneous and transdermal delivery of FAAEs. Furthermore, medium-chain coconut oil-derived FAAEs exhibited faster diffusion rates compared to sunflower oil-based FAAEs with long-side acyl residues, including the commonly applied ascorbyl palmitate. Experimental data were successfully fitted using the Peppas and Sahlin model, which accounted for a lag phase and the combined effect of Fickian diffusion and polymer relaxation. In the case of long-chain esters, the lag phase was prolonged, and the calculated effective diffusion coefficients (Deff) were lower compared to medium-chain FAAEs. Accordingly, the highest Deff value was observed for ascorbyl caprylate, being even 60 times higher than for ascorbyl palmitate. These results suggest the emerging potential of emulgel with incorporated coconut oil-derived FAAEs for efficiently delivering vitamin C into the skin.

Preparation, characterization, and mechanism of swelling and Cu2+ adsorption by alginate-based beads enhanced with Huangshui polysaccharides

As biomass resources, Huangshui (HS) is a high-yield by-product from the traditional solid-state fermentation of Chinese Baijiu. This study aims to sustainably utilize crude HS polysaccharide (cHSP) to prepare alginate-based beads for promoting Cu2⁺ adsorption in the wastewater and explore the relative mechanism. Sodium alginate/Fe3O4 (Mag-SA) beads were synthesized via Ca2+-induced crosslinking, while Mag-SA-cHSP beads were created by immobilizing cHSP into Mag-SA matrix. The chemical structure, physical properties, and morphology of the beads were analyzed using FTIR, SEM-EDS, XRD, VSM, TGA, Zetasizer, and XPS, respectively. The swelling performance, adsorption ability, kinetic and thermodynamic characteristics, etc. were conducted to better elucidate the mechanism of Cu2⁺ adsorption enhancement by cHSP. Results showed that 1.0 wt% cHSP addition provided a stable three-dimensional structure and enhanced thermal stability, swelling performance, and adsorption ability. The swelling ratio increased from 75.29 g/g to 86.56 g/g after cHSP incorporated into the beads, which was driven by water diffusion and chain relaxation. The Cu2+ adsorption capacity improved from 59.10 mg/g to 67.89 mg/g after cHSP embedded into the beads, which involved ion-exchange, chelation, and electrostatic interaction. Additionally, the beads retained 66%–71% of their initial adsorption capacities after four adsorption-desorption cycles, indicating the possibility of repeated use to reducing costs. This work presents a novel approach to enhancing the utilization value of Huangshui and developing a reusable and efficient material for heavy metal ion removal from wastewater in an eco-friendly manner.

Thermodynamics and kinetics of cation partitioning between plagioclase and trachybasaltic melt in static and dynamic systems: A reassessment of the lattice strain and electrostatic energies of substitution

Most of the solidification history of magmas beneath active volcanoes takes place in chemically and physically perturbed plumbing systems where the growth of crystals is collectively governed by a range of kinetic processes related to the dynamics of crustal reservoirs and eruptive conduits. In this context, we have experimentally investigated the partitioning of major, minor, and trace cations between plagioclase and trachybasaltic melt under conventional static (no physical perturbation) and dynamic (melt stirring) crystallization regimes. Slow interface reaction kinetics are established between the advancing crystal surface and the adjacent melt, as the result of the combined control of a small degree of effective undercooling, prolonged diffusive relaxation, and convective homogenization. The kinetic aspects of plagioclase growth influence the partitioning of trace cations during transport of structural units across the crystal-melt interface, with consequent departure from macroscopic equilibrium in the system. The type and number of charge–balanced and −imbalanced configurations produced by the accommodation of trace cations into the coordination polyhedron can be thermodynamically rationalized in terms of lattice strain and electrostatic partitioning energetics. However, the overall solution energy accompanying trace cation kinetic substitutions cannot be entirely deconvoluted from major component activities in both melt and plagioclase phases. The emerging view that slow interface kinetic processes may lead to strong compositional dependence for the partition coefficient in dynamic subvolcanic environments contrasts markedly with the conventional idea that the energetics of cation partitioning are dominantly controlled by the effect of isothermal changes in the bulk system.

Re-evaluating the diffusivity of phosphorus in olivine: Implications of low diffusive mobility for thermochronology

Heterogeneities in the phosphorus (P) content of olivine are relatively resistant to diffusive homogenization when compared with other compositional heterogeneities. Thus, heterogeneities in the spatial distribution of P can preserve petrological information about olivine crystals from the earliest stages of crystallization which have been otherwise eliminated. However, compared to independent determinations of protracted cooling timescales in slowly cooled rocks, P enrichments are so sharp as to suggest a rate of diffusive mobility that is many orders of magnitude slower than previously suggested. Here, we heat single natural olivine crystals with sharply defined P heterogeneities (0.02–0.15 wt% P2O5 over 0.5 μm spatial scale) in a 1-atmosphere gas-mixing furnace for durations of 10–20 days at 1400°C, thus exposing them to conditions that should be sufficient for complete diffusive relaxation according to published P diffusivity values. However, high-precision chemical analysis of the same interior section before and after heating reveals no discernable difference in the sharpness of phosphorus concentration patterns. Therefore, diffusion chronometry applied to skeletal P enrichments in olivine currently provides erroneously short diffusive timescales. We discuss several possible causes for these discrepancies and the implications for diffusion chronometry as applied to phosphorus in olivine.

Effect of polyelectrolyte (PAA) on the dynamics of weakly charged microemulsion droplets in acidic medium

We use the dynamic light scattering technique (DLS) to study the dynamic behavior of complex constituted by weakly charged microemulsion in the presence of polyelectrolyte. We investigated the impact of adding oppositely charged polyacid (PAA), which is a pH-dependent polyelectrolyte, on the dynamics of charged microemulsion nanodroplets in an acidic medium at pH = 4.5 when the polyacrylic acid are partially charged. In a diluted regime, two diffusive relaxation modes are seen when adding (upon addition) the polyacrylic acid PAA to the microemulsion nanodroplets due to collective diffusion and self-diffusion fluctuations. In the concentrated regime, we observed three diffusive relaxation modes when charged microemulsion nanodroplets complexed with oppositely charged polyacrylic acid. We attribute the two first relaxation modes to the collective diffusion (fluctuation of concentration) and self-diffusion of the microemulsion nanodroplets. The third mode which is a slower relaxation mode; we attribute this relaxation process to the motion of the network formed by the polyacid PAA and microemulsion nanodroplets, or “breathing mode” of the network.

Anomalous relaxation and hyperuniform fluctuations in center-of-mass conserving systems with broken time-reversal symmetry.

We study the Oslo model, a paradigm for absorbing-phase transition, on a one-dimensional ring of L sites with a fixed global density ρ[over ¯]; we consider the system strictly above critical density ρ_{c}. Notably, microscopic dynamics conserve both mass and center of mass (CoM), but lack time-reversal symmetry. We show that, despite having highly constrained dynamics due to CoM conservation, the system exhibits diffusive relaxation away from criticality and superdiffusive relaxation near criticality. Furthermore, the CoM conservation severely restricts particle movement, causing the mobility-a transport coefficient analogous to the conductivity for charged particles-to vanish exactly. Indeed, the steady-state temporal growth of current fluctuation is qualitatively different from that observed in diffusive systems with a single conservation law. Remarkably, far from criticality where the relative density Δ=ρ[over ¯]-ρ_{c}≫ρ_{c}, the second cumulant, or the variance, 〈Q_{i}^{2}(T,Δ)〉_{c}, of current Q_{i} across the ith bond up to time T in the steady-state saturates as 〈Q_{i}^{2}〉_{c}≃Σ_{Q}^{2}(Δ)-constT^{-1/2}; near criticality, it grows subdiffusively as 〈Q_{i}^{2}〉_{c}∼T^{α}, with 0<α<1/2, and eventually saturates to Σ_{Q}^{2}(Δ). Interestingly, the asymptotic current fluctuation Σ_{Q}^{2}(Δ) is a nonmonotonic function of Δ: It diverges as Σ_{Q}^{2}(Δ)∼Δ^{2} for Δ≫ρ_{c} and Σ_{Q}^{2}(Δ)∼Δ^{-δ}, with δ>0, for Δ→0^{+}. Using a mass-conservation principle, we exactly determine the exponents δ=2(1-1/ν_{⊥})/ν_{⊥} and α=δ/zν_{⊥} via the correlation-length and dynamic exponents, ν_{⊥} and z, respectively. Finally, we show that in the steady state the self-diffusion coefficient D_{s}(ρ[over ¯]) of tagged particles is connected to activity through the relation D_{s}(ρ[over ¯])=a(ρ[over ¯])/ρ[over ¯].

Non-reversible lifts of reversible diffusion processes and relaxation times

AbstractWe propose a new concept of lifts of reversible diffusion processes and show that various well-known non-reversible Markov processes arising in applications are lifts in this sense of simple reversible diffusions. Furthermore, we introduce a concept of non-asymptotic relaxation times and show that these can at most be reduced by a square root through lifting, generalising a related result in discrete time. Finally, we demonstrate how the recently developed approach to quantitative hypocoercivity based on space–time Poincaré inequalities can be rephrased and simplified in the language of lifts and how it can be applied to find optimal lifts.

Development and Characterisation of deep Eutectic Mixture of the Atorvastatin Calcium for Oral Drug Delivery

The poor aqueous solubility and low oral bioavailability of atorvastatin calcium pose significant challenges in optimising its therapeutic efficacy. This study explores the formulation of deep eutectic solvents (DES) to enhance the solubility and bioavailability of atorvastatin calcium for oral delivery. Various DES formulations were prepared using choline chloride, choline bitartrate, and selected carboxylic acids. The formulations were characterised through physicochemical analysis, including pH, drug content, particle size, zeta potential, and Fourier-transform infrared spectroscopy. The most promising formulation, F12, exhibited a yellowish transparent appearance, a mean particle size of 74.21 nm, and a zeta potential of -22.3 mV, indicating good colloidal stability. In vitro drug release studies revealed a delayed release profile for F12 compared to the pure drug, potentially offering advantages in prolonged therapeutic effect and reduced dosing frequency. Kinetic modelling analysis suggested a diffusion-controlled release mechanism influenced by drug diffusion and polymer relaxation. Overall, this study demonstrates the potential of DES formulations in enhancing the solubility and bioavailability of atorvastatin calcium, paving the way for improved therapeutic outcomes and patient compliance.

40Ar diffusion in phlogopite: [formula omitted] atomistic calibration and implications for Ar–melt–solid kinetic interactions and ascent dynamics of mantle xenoliths and kimberlites

40Ar/39Ar ages of phlogopite from kimberlite-hosted mantle xenoliths are commonly older than the kimberlite eruption, despite the fact that argon is supposed not to be retained by phlogopite at temperatures above hydrothermally-derived Ar closure temperatures (<500°C). Combining Molecular Dynamics (MD) with Nudged Elastic Band (NEB) and Transition State Theory (TST), we investigate 40Ar−PVT (Pressure−Volume−Temperature) relationships in pristine, defect-free, phlogopite and show that 40Ar diffusivity is several orders of magnitude slower than existing estimates with a strong effect of pressure on diffusion rates and retention of 40Ar at mantle conditions. These results imply to fundamentally revise residence- and transit-time estimates based on Ar kinetics in phlogopite assuming simple diffusive relaxation during upwelling. When accounting for pressure, 40Ar retention trends in phlogopite predict substantially slower kimberlite ascent rates than documented by independent chronometers, indicating that 40Ar resetting during ascent in phlogopite does not result from simple decompression-driven diffusive relaxation. We argue that 40Ar remobilization probably involves secondary structural–textural modifications induced by reaction-driven recrystallization or rim overgrowth. These findings have far-reaching consequences in terms of argon isotopic mobility at mantle depths as well as for dating and tracing metasomatic events during crust−mantle interactions in the evolution of the subcontinental mantle.