Permeation Enhancers Research Articles

Development of nanoemulgel of 5-Fluorouracil for skin melanoma using glycyrrhizin as a penetration enhancer

The purpose of this study was to enhance the topical delivery of 5-Fluorouracil (5-FU), a cancer treatment, by developing a nanoemulgel formulation. Glycyrrhizin (GLY), a natural penetration enhancer has been investigated to exhibit synergistic effects with 5-FU in inhibiting melanoma cell proliferation and inducing apoptosis, Hence, GLY, along with suitable lipids was utilized to create an optimized nanoemulsion (NE) based gel. Solubility studies and ternary phase diagram revealed isopropyl myristate (IPM), Span 80, Tween 80 as Smix and Transcutol P as co-surfactant. IPM demonstrates excellent solubilizing properties facilitates higher drug loading, ensuring efficient delivery to the target site.,The optimized formulation consisting of 40 % IPM, 30 % of mixture of Tween80: Span80 (Smix) and 15 % Transcutol P provides with a nanometric size of 64.1 ± 5.13 nm and drug loading of 97.3 ± 5.83 %. The optimized formulation observed with no creaming and breakeing of NE and found thermodynamically stable during different stress conditions (temperatures of 4.0 °C and 45.0 °C) and physical thawing (−21.0 ± 0.50 °C to 20.0 ± 0.50 °C). The NE was then transformed into a nanoemulgel (NEG) using 1.5 % w/w Carbopol base and 0.1 % w/w glycyrrhizin. The ex vivo permeability studies showed significant enhancements in drug permeability with the GLY-based 5-FU-NEG formulation compared to pure 5-FU gel in excised pig skin upto1440 min in PBS 7.4 as receptor media. The IC50 values for Plain 5-FU gel, 5-FU-NEG, and GLY-based 5-FU-NEG were found to be 20 µg/mL, 1.1 µg/mL, and 0.1 µg/mL, respectively in B16F10 cell lines. The percentage intracellular uptake of GLY-5-FU-NEG and 5-FU-NEG was found to be 44.3 % and 53.6 %, respectively. GLY-based 5-FU-NEG formulation showed alterations in cell cycle distribution, in compared to 5-FU-NE gel. The overall findings suggest that the GLY-based 5-FU-NEG holds promise for improving anti-melanoma activity.

Enhancing extracellular monascus pigment production in submerged fermentation with engineered microbial consortia

In this study, we investigated the impact of microbial interactions on Monascus pigment (MP) production. We established diverse microbial consortia involving Monascus purpureus and Lactobacillus fermentum. The addition of Lactobacillus fermentum (4% at 48 h) to the submerged fermentation of M. purpureus resulted in a significantly higher MP production compared to that achieved using the single-fermentation system. Co-cultivation with immobilized L. fermentum led to a remarkable increase of 59.18% in extracellular MP production, while mixed fermentation with free L. fermentum caused a significant decrease of 66.93% in intracellular MPs, contrasting with a marginal increase of 4.52% observed during co-cultivation with immobilized L. fermentum and the control group respectively. The findings indicate an evident enhancement in cell membrane permeability of M. purpureus when co-cultivated with immobilized L. fementum. Moreover, integrated transcriptomic and metabolomic analyses were conducted to elucidate the regulatory mechanisms underlying MP biosynthesis and secretion following inoculation with immobilized L. fementum, with specific emphasis on glycolysis, steroid biosynthesis, fatty acid biosynthesis, and energy metabolism.

Efficiency of NZ2114 on Superficial Pyoderma Infected with Staphylococcus pseudintermedius.

Staphylococcus pseudintermedius (S. pseudintermedius) is the main pathogen causing pyoderma of canines. With the emergence of drug-resistant bacteria, traditional antibiotic treatments are limited. As a potential antibacterial agent, NZ2114 was effective against S. pseudintermedius, including drug-resistant strains. Its bactericidal efficacy was superior to mupiroxacin, ofloxacin and lincomycin. To facilitate the transcutaneous delivery of NZ2114 for the treatment of superficial pyoderma, chemical permeation enhancers were added since water-soluble NZ2114 does not easily penetrate the skin lipid layer. Two different NZ2114 sprays were prepared by combining 1% Azone + 10% propylene glycol (PG) or 5% N-methylpyrrolidone (NMP) + 10% PG with NZ2114 after screening. The cumulative permeability of NZ2114 sprays were 244.149 and 405.245 μg/cm2 at 24 h with an in vitro percutaneous assay of mice skin, which showed a 244% and 405% increase in skin permeability than NZ2114, respectively. In addition, the efficacy of NZ2114 sprays in reducing skin bacteria colonisation was demonstrated in a mouse model of superficial pyoderma (24 mice, 3 mice/group) induced by S. pseudintermedius, and the 5% NMP + 10% PG + NZ2114 group had the best therapeutic effect compared to the other groups. This preparation did not cause any skin irritation, laying the foundation for the development of an effective and non-toxic topical product.

Partial melting in polycrystalline ice: pathways identified in 3D neutron tomographic images

Abstract. In frozen cylinders composed of deuterium ice (Tm+3.8 ∘C) and 10 % water ice (Tm 0 ∘C), it is possible to track melt pathways produced by increasing the temperature during deformation. Raising the temperature to +2 ∘C produces water (H2O) which combines with the D2O ice to form mixtures of HDO. As a consequence of deformation, HDO and H2O meltwater are expelled along conjugate shear bands and as compactional melt segregations. Melt segregations are also associated with high-porosity networks related to the location of transient reaction fronts where the passage of melt-enriched fluids is controlled by the localized ductile yielding and lowering of the effective viscosity. Accompanying the softening, the meltwater also changes and weakens the crystallographic fabric development of the ice. Our observations suggest meltwater-enriched compaction and shear band initiation provide instabilities and the driving force for an enhancement of permeability in terrestrial ice sheets and glaciers.

Effect of ursodiol on alginate/PLL nanoparticles with non-ionic surfactant for gene delivery

Hearing loss is a widespread condition, affecting people from a range of demographics. Gene therapy is an emerging method for the amelioration of this condition. Challenges associated with the delivery of genes to various sites within the ear remain a significant challenge. In the present work, a novel polymer nanoparticle delivery system was developed, incorporating a bile acid excipient. Bile acids have previously been shown to improve drug delivery through their permeation enhancing properties; however, few studies report their use in gene delivery systems. Nanoparticles were developed with sodium alginate and poly-L-lysine through an ionotropic gelation method. Various surfactants including Tween-80 and poly-ethylene glycol 6000 were incorporated to both improve the solubility of the bile acid, ursodiol, and to modify nanoparticle properties. The evaluation of the nanoparticle’s safety profiles was the primary outcome of this study. The secondary aims were to perform genetic studies, such as transfection efficiency. The nanoparticles generated in this study demonstrated formulation-dependent variability in particle size ranging from 30 to 300 nm. Several of the developed formulations demonstrated suitable safety profiles; further, the introduction of bile acid helped to reduce toxicity. Transfection efficiency for all formulations remained low, potentially due to poor plasmid release inside the cell. Poor transfection efficiency is one of the key pitfalls associated with polymer nanoparticles Overall the present study developed nanoparticles with suitable safety profiles but limited efficacy. The use of modified polymers, additional excipients, and cell-targeting peptides are potential methods that may be explored in future studies to help further improve gene delivery.

Chaenomeles sinensis Extract Ameliorates Ovalbumin-Induced Allergic Rhinitis by Inhibiting the IL-33/ST2 Axis and Regulating Epithelial Cell Dysfunction.

Chaenomeles sinensis has traditionally been used as an herbal medicine due to its characteristics that protect against inflammation, hypertension, and mutagenesis. However, the effect of Chaenomeles sinensis extract (CSE) on allergic rhinitis (AR) and its underlying mechanisms have yet to be thoroughly investigated. The current study explored the likely effect of CSE on AR in an ovalbumin (OVA)-induced AR mouse model. To this end, OVA-specific immunoglobulins, nasal symptoms, cytokine production, the infiltration of inflammatory cells, and nasal histopathology were assessed to determine the role of CSE against AR. The supplementation of CSE was found to suppress OVA-specific IgE, while OVA-specific IgG2a was increased in the serum. Further, CSE ameliorated the production of T helper type 2 (Th2) cytokines whereas it increased Th1 cytokine levels in nasal lavage fluid. Moreover, the CSE treatment group exhibited significant inhibition of IL-33/ST2 signaling. Subsequently, CES reversed the OVA-induced enhancement of epithelial permeability and upregulated E-cadherin, thus indicating that CES plays a protective role on epithelial barrier integrity. Altogether, the oral administration of CSE effectively controlled allergic response by restricting the buildup of inflammatory cells, enhancing nasal and lung histopathological traits, and regulating cytokines associated with inflammation. Collectively, the results show that the supplementation of CSE at different doses effectively regulated AR, thus suggesting the therapeutic efficiency of CSE in suppressing airway diseases.

Dissemination of antibiotic resistance genes is regulated by iron oxides: Insight into the influence on bacterial transformation

The transportation of antibiotic resistance genes (ARGs) in manure-soil-plant continuums poses risks to human health. Horizontal gene transfer, particularly for bacterial transformation, is an important way for ARG dissemination. As crucial components in soils, iron oxides impacted the fates of various abiotic and biotic contaminants due to their active properties. However, whether they can influence the transformation of ARGs is unknown, which waits to be figured out to boost the assessment and control of ARG spread risks. In this study, we have investigated the effects of goethite, hematite, and magnetite (0–250 mg/L, with sizes < 100 nm and > 100 nm) on the transfer of ampicillin resistance genes to Escherichia coli cells. At lower iron oxide concentrations, the transformation of ARGs was first facilitated (transformation frequency reached up to 3.38-fold higher), but the facilitating effects gradually weakened and eventually disappeared as concentrations further increased. Particle size and iron oxide type were not the universal determinants controlling the transformation. At lower concentrations, iron oxides interacted with proteins and phospholipids in E. coli envelope structures, and induced the overgeneration of intracellular reactive oxygen species. Consequently, they led to pore formation and permeability enhancement on the cell membrane, thus promoting the transformation. The facilitation was also associated with the carrier-like effect of iron oxides for antibiotic resistance plasmids. At higher concentrations, the weakened facilitations were attributed to the aggregation of iron oxides. In this study, we highlight the crucial roles of the concentrations (contents) of iron oxides on the dissemination of ARGs in soils; this study may serve as a reference for ARG pollution control in future agricultural production.

Cracks Propagation and Permeability Enhancement Caused by Supercritical CO2 and Water Fracturing in Natural Coal–Rock Combination

Cracks Propagation and Permeability Enhancement Caused by Supercritical CO₂ and Water Fracturing in Natural Coal–Rock Combination

Hydrogel/mineral-integrated interface for synergistic antifouling membrane

Antifouling performance is significant for practical membrane separation, determining the membrane permselectivity, lifespan and maintenance cost. Integrating multi-component antifouling materials at the membrane interface is a promising solution for maximizing the membrane antifouling potential. Herein, a gel-mineral hybrid interface was constructed on polyvinylidene fluoride (PVDF) membrane via MnO2 mineralization induced by the tannic acid (TA)/polyvinylpyrrolidone (PVP) intermediate hydrogel layer. The resultant membrane exhibited superhydrophilicity and resulted in excellent enhancement in permeability and antifouling performance. The modified ultrafiltration membrane exhibited enhanced water flux, rejection of pollutants, and flux recovery rate (FRR) for organic solutions. The pure water flux of the optimal membrane is 40 % higher than that of PVDF. Most importantly, this hydrogel/mineral hybrid interface collectively resists the adhesion of pollutants and catalytic cleaning to remove pollutants. This integrated interface tailoring strategy paves a way for multi-scale antifouling separation membranes.

Acidification-Induced Micronano Mechanical Properties and Microscopic Permeability Enhancement Mechanism of Coal.

An acid solution improves the pore-plugging problem in hydraulic fracturing, which in turn improves the permeability of the coal seam. The study aimed to investigate the effect of mixed acid on the micronano mechanical properties and permeability of the coal seam. The surface morphology of acidified coal was analyzed from the micronano scale using atomic force microscopy (AFM) and scanning electron microscopy. Additionally, the micronano scale mechanical characteristics of acidified coal were examined using the mechanical mode in an atomic force microscope. Furthermore, the complexity and connectivity of the micronano pores of samples were investigated using the low-temperature nitrogen adsorption and mercury intrusion porosimetry methods and the fractal theory. The results indicated that the surface minerals of acidified coal were dissolved, loosening the coal and increasing the complexity of the pore structure. Mineral deformation and pore deformation weakened the mechanical properties of coal at the micronano scale, and the mean elastic modulus of acidified coal (B# and E#) decreased by 28.78 and 25.66% compared to that of raw coal. The acid solution effectively enlarged the pore diameter, transitioning from micropores to mesopores and macropores, and the total pore volume of acidified coal increased by 1.88 times and 1.25 times, Kn increased from 0.064 to 0.581 and 0.37, respectively. The type of methane diffusion in the diffusion pores changed from Knudsen diffusion to transition-type diffusion. The tortuosity of the pore structure of acidified coal decreased, the fractal dimension of the tortuosity of the pore structure decreased, and the permeability increased by nearly three times. The research results indicate that the mechanical properties of coal decrease after acidification and that the microstructural changes can promote methane migration (diffusion-seepage), which can provide theoretical guidance for coalbed methane extraction in low-permeability coal reservoirs.

Versatile Nanoparticulate Systems as a Prosperous Platform for Targeted Nose-Brain Drug Delivery.

The intranasal route has proven to be a reliable and promising route for delivering therapeutics to the central nervous system (CNS), averting the blood-brain barrier (BBB) and avoiding extensive first-pass metabolism of some drugs, with minimal systemic exposure. This is considered to be the main problem associated with other routes of drug delivery such as oral, parenteral, and transdermal, among other administration methods. The intranasal route maximizes drug bioavailability, particularly those susceptible to enzymatic degradation such as peptides and proteins. This review will stipulate an overview of the intranasal route as a channel for drug delivery, including its benefits and drawbacks, as well as different mechanisms of CNS drug targeting using nanoparticulate drug delivery systems devices; it also focuses on pharmaceutical dosage forms such as drops, sprays, or gels via the nasal route comprising different polymers, absorption promoters, CNS ligands, and permeation enhancers.

Groundwater Hydraulics in Increased Spring Discharge following Earthquakes: Some Applications and Considerations

Earthquakes often entail alterations in the groundwater flow regime, in the phreatic level, surges and losses of springs, and the discharge in brooks. A variety of theoretical approaches attempt to elucidate the post-earthquake effects on spring discharge. This study adopts a conceptual approach, primarily presenting diverse methods to estimate water released by earthquakes involving calculations of discharge surpluses in springs. This study delves into refined techniques rooted in groundwater hydraulics, displaying applications of analytical and simulation methodologies to quantify earthquake-induced groundwater discharge in springs. This research investigates springs as natural indicators and applies mathematical precipitation–runoff models, particularly the CREC model, to simulate hydrographs in post-earthquake scenarios. We apply analytical procedures or mathematical simulation techniques employed in groundwater hydraulics for natural aquifer recharge calculations. Firstly, we briefly describe the methods based on the analysis of depletion curves of hydrographs in spring discharge. Additionally, specific mathematical rainfall–runoff models used to simulate hydrographs of karstic springs, along with derived analytical approximations, are adapted for this scenario. These hydraulic calculations involve the depletion coefficient and hydrodynamic volumes of aquifers, parameters that reveal certain aspects of the relation between groundwater and earthquakes. Three main features are: (a) Acknowledging faults as the primary geological structures in transmitting pore pressures due to earthquakes. Thus, for large and deep faults, which connect the ground surface with the Earth’s crust bottom—where earthquakes trigger—the depletion coefficient, α, usually reaches high values (α = 0.1 days−1). Therefore, these faults become more sensitive to pore pressure than other lithologies. (b) Elucidating the mechanisms of permeability enhancement caused by earthquakes. (c) Highlighting the substantial volumes in motion within the Earth’s interior, which, for instance, could constitute a significant source for the origin of mineral deposits. Mathematical calculations enable the determination of the volume of mobilized water that can be discharged by gravity in each earthquake. This, along with its recurrence, justifies the substantial mineralization volumes.

Circumventing the Gastrointestinal Barrier for Oral Delivery of Therapeutic Proteins and Peptides (PPTs): Current Trends and Future Trajectories.

Therapeutic proteins and peptides (PPTs) have become one of the most important biological molecules for the management of many common and complex diseases due to their high specificity and high bioactivity. However, these biomolecules are mainly given by the hypodermic injection, which often leads to poor patient compliance due to the invasive nature of this route of administration. The oral route has been considered the most convenient and patient-friendly route for drug delivery relative to hypodermic injection. Despite the ease and simplicity conferred by oral administration, this drug delivery route suffers rapid peptide degradation in gastric fluid and low intestinal uptake. In order to circumvent these issues, several strategies, such as enzyme inhibitors, permeation enhancers, chemical modification, mucoadhesive and stimuli-responsive polymers, and specialised particulate formulation have been developed. Such strategies are designed with the aim of protecting proteins and peptides from the harsh gastrointestinal environment as well as providing a strategy to enhance the uptake of the therapeutic across the gastrointestinal tract. This review aims to provide an overview of the current development in enteral drug delivery strategies for proteins and peptides. The design of these drug delivery systems in overcoming physical and chemical barriers along the gastrointestinal tract while improving oral bioavailability will be highlighted and discussed.

Fabrication, Optimization, and Evaluation of Transdermal Patch: As an Alternative and Effective Transdermal Delivery System for Nebivolol HCl.

Nebivolol HCl is a unique third-generation beta blocker that has less oral bioavailability and exhibits various adverse effects like gastrointestinal disturbance and abdominal pain. This study aimed to formulate and evaluate nebivolol HCl transferosomal transdermal patches to reduce the problems associated with oral delivery of the drug and enhancement of drug permeation through the skin. Nebivolol HCl loaded transferosomes were prepared by thin film hydration method. Eight formulations were prepared based on the two independent variables, type of surfactant (Tween 80 and Span 80) and Phospholipid: Edge activator ratio and were evaluated for their vesicle size, PDI, and entrapment efficiency. The optimized formulations were incorporated into transdermal patches, which were evaluated for physicochemical properties, in-vitro and ex-vivo permeation, skin irritancy, and stability studies. The vesicle size of the transferosomes ranged from 49nm to 93nm, and EE% varied from 39% to 79%. Vesicles formed with Span 80 as an edge activator showed smaller vesicle size and greater EE% as compared to Tween 80. Based on the results, TW4 and SP4 were selected as the optimized formulations for further incorporation into the transdermal patches. In-vitro and ex-vivo permeation studies showed permeation in the order F2 > F3 > F1, indicating that transferosomal formulations showed superior permeation of the drug compared to plain Nebivolol HCl patches. Span 80 transferosomes showed a slightly better permeation than Tween 80. Stability studies showed that transferosomes and the transdermal patches demonstrated good stability under proper storage conditions. The study concluded that transferosomal patches of Nebivolol HCl could be used as a potential approach with effective transdermal delivery for the management of hypertension.

Reactive Transport Process of Earthquake‐induced Hydro‐chemical Changes in Guanding Thermal Spring, Western Sichuan, China

AbstractEarthquake‐related hydrochemical changes in thermal springs have been widely observed; however, quantitative modeling of the reactive transport process is absent. In the present study, we apply reactive transport simulation to capture the hydrochemical responses in a thermal spring following the Wenchuan Ms 8.0 and Lushan Ms 7.0 earthquakes. We first constrain deep reservoir geothermal fluid compositions and temperature by multicomponent geothermometry, and then a reactive geochemical transport model is constructed to reproduce the hydrochemical evolution process. The results show that the recharge from the shallow aquifer increases gradually until it reaches a peak because of the permeability enhancement caused by the Lushan earthquake, which may be the mechanism to explain the earthquake‐related hydrochemical responses. In contrast to the postseismic effect of the Wenchuan earthquake, the chemical evolution can be considered as hydrochemical anomalies related to the Lushan earthquake. This study proves that the efficient simulation of reactive transport processes is useful for investigating earthquake‐related signals in hydrochemical time series.

Formulation and Optimization of Nanoemulsions Loaded with Gamma−Aminobutyric Acid (GABA) for Dermatological Application: Assessing Skin Permeation and Penetration Enhancement

Gamma−aminobutyric acid (GABA) presents several potential skin benefits, but its water−soluble nature poses challenges for effectively penetrating the skin to produce its effects. This research aimed to improve GABA’s skin penetration and availability by employing a nanoemulsion formulation, both with and without the aid of the penetration enhancer 1,8−cineole. Using a high−pressure homogenizer, an oil−in−water nanoemulsion was created, and its size and distribution were analyzed. The stability of these nanoemulsions was tested under various conditions, revealing their resilience over six months, even at elevated temperatures of 40 °C. In vitro tests on pig skin showed that GABA−loaded nanoemulsions, particularly those without the enhancer, demonstrated a nearly 2.89−fold increase in skin permeation compared to the solution form. Moreover, the addition of the enhancer amplified this effect, resulting in over a 3.37−fold increase in skin permeation compared to the solution. These results emphasize the potential of nanoemulsion formulations as effective tools for enhancing GABA’s skin permeation and availability, potentially expanding its use in dermatological applications. Further exploration and research are necessary to fully exploit GABA’s capabilities in supporting skin health and wellness.

How do salt additives improve the permeability of the thin-film composite membrane?

Various salt additives were widely used to enhance the permeability of thin-film composite (TFC) membranes. Researchers attributed the improvement in TFC membranes to the change in the polyamide (PA) layer. However, the contribution degree of PA layer to TFC membrane permeability enhancement and the effect of salt additives on the substrate are ambiguous. In this study, the effect of salt additives on the permeation resistance of FTC membranes was analyzed. The results showed that the salt additives could reduce both the permeation resistance of the PA layer and substrate, but the effect on the substrate was more pronounced. For example, after adding NaCl, the permeation resistance of the substrate in the heat curing membrane reduced from 0.1764 to 0.0201 bar h m−1, which was much more than that in the PA layer. This study revealed a new mechanism of salt additives improving the permeability of TFC membranes and deepened the understanding of the action mechanism of salt additives.

Control of gas selectivity and permeability through COF-GO composite membranes for sustainable decarbonization and hydrogen production

A promising way to address modern environmental and energy supply challenges is via rapid implementation of decarbonization and hydrogen production technologies. Development of gas separation membranes with high selectivity and permeability is essential for these processes but is still a bottleneck. Our research focuses on achieving precise control of gas diffusion pathways through on-demand regulation of material interactions in thin composite membranes. We combine 2D covalent organic frameworks (COFs) and graphene oxide (GO) to create COF-GO composite membranes with desirable nanosheet stacking, controllable thicknesses and pathways for gases. By pH-assisted self-assembly, we fine-tune material interactions and achieve simultaneous enhancement of permeability and selectivity by increasing membrane thickness and regulating the interactions between COF and GO nanosheets by pH. At a thickness of 1.3 μm, the COF-GO membrane, assembled under pH 4, demonstrates good working characteristics for H2/CO2 equimolar mixture (at room temperature and 1 bar), with a H2 permeability of 366 Barrer, selectivity of 15.6, and long-term stability exceeding 200 h. This work paves the way for tailored, performing gas separation with long-term stability. It guides the unique 2D transport mechanism to be utilized under practical conditions. Our research offers a novel strategy for the design of composite membranes from two-dimensional (2D) materials for gas separation technologies. It contributes to sustainable decarbonization and hydrogen production solutions, bringing us closer to a greener, more environmentally friendly future.

Influence of subsurface temperature on cryogenic fracturing efficacy of granite rocks from Kazakhstan

Liquid nitrogen (LN2) is a new stimulation technology suitable for geothermal energy extraction that increases porosity, permeability, and overall contact area in candidate subsurface formations. It is considered appropriate for hot dry rock (HDR) reservoirs. Due to the significant temperature difference between hot rock and cryogenic fluid, extensive thermally induced cracking is anticipated upon contact, which is helpful in future water-steam cycling operations. To examine the degree of rock integrity failure in granite samples as a function of exposure mode, different procedures were followed for comparison. In particular, three commercial granite samples from three regions of Kazakhstan: Kapal-Arasan, Zhylgyz, and Zheltau, were heated to various elevated temperatures prior to immersion in LN2 with variations in freezing time (FT) and numbers of freezing-thawing cycles (FTC). Samples were examined by various methods to quantify the impact of the cryogenic fracturing process. Compression, acoustic emission (AE), and permeability tests were performed on granite with different starting temperatures ranging from 200 °C to 500 °C. Permeability enhancement was generally in the range of 50-90 %. Scanning electron microscopy (SEM) was also used to document the microscopic characteristics of thermally-induced cracks and indicated most induced fractures to be microscale features. Results showed reductions in Unconfined Compressive Strength of LN2-treated samples by up to 76 %. The experimental outcomes demonstrate that LN2 cooling of hot granite induces mechanical rock failure and permeability augmentation. Furthermore, the degree of thermo-fracturing increases with temperature difference and time of LN2 treatment in both freezing time and freezing-thawing cycle methods. This is the first systematic study of its kind to test three commercially available granites from Kazakhstan with this combination of examination tools to assess alternate cryo-fracturing methods for geothermal energy prospecting and contact area enhancement.

Interaction between Permeation Enhancers and Lipid Bilayers.

Permeation enhancers (PEs) are a class of molecules that interact with the epithelial membrane and transiently increase its transcellular permeability. Although there have been few clinical trials of PE coformulated drugs, the mechanism of action of PEs remains elusive. In this paper, the interaction between two archetypes of PEs [salcaprozate sodium (SNAC) and sodium caprate (C10)] and membranes is investigated with extensive all-atom molecular dynamics simulations. The simulations show that (1) the association between the neutral PEs and membranes is favored in free energy, (2) the propensity of neutral PE aggregation is larger in aqueous solution than in lipid bilayers, (3) the equilibrium distribution of neutral PEs in membranes is fast, e.g., accessible with unbiased MD simulations, and (4) the micelle of neutral PEs formed in aqueous solution does not rupture the membranes (e.g., not forming pores or breaking up the membrane) under simulation conditions. All results combined, this study indicates that PEs insert into the membranes in an equilibrium or near equilibrium process. This study lays the foundation for future investigations of how PEs impact the free energy of permeation for small molecules.