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1.
Food Res Int ; 188: 114467, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823836

ABSTRACT

Cellulose-based packaging has received great attention due to its characteristics of biodegradability, sustainability, and recyclability. Natural polymer coatings are usually applied to the paper surface to enhance the barriers to water vapour and improve the mechanical properties. A chitosan-based coating for paper packaging was developed in this work to store specialty roasted coffee beans, evaluating two samples of chitosan (Sigma® and molasses chitosan), and following the physico-chemical and microbiological characteristics of coffee beans along a period of 60 days. Sensory tests (Ranking Descriptive Analysis and Preference Test) were applied to the beverage prepared with the roasted and ground coffee beans stored in each packaging. Thin chitosan films provided good coverage and adhesion on the paper. Improved mechanical properties and lower water permeability were observed in the chitosan-coated papers. The physicochemical and microbiological characteristics of the coffee beans were not influenced by the packaging along 60 days of storage. The molasses chitosan coating resulted in slightly darker roasted beans. In sensory evaluation, there is a clear difference between the chitosan samples, so that molasses chitosan-coated packaging had higher scores compared to Sigma® chitosan treatment for flavor and global impression in the preference analysis of the beverage. The molasses chitosan-coated packaging had three to four more consumers attributing the highest scores for the beverage prepared with the roasted beans stored in this type of packaging.


Subject(s)
Chitosan , Food Packaging , Paper , Chitosan/chemistry , Food Packaging/methods , Coffee/chemistry , Beverages/analysis , Seeds/chemistry , Seeds/microbiology , Humans , Taste , Coffea/chemistry , Coffea/microbiology , Consumer Behavior , Permeability
2.
Food Res Int ; 188: 114496, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823843

ABSTRACT

Agro-industrial co-products, such as fish gelatin, stand out for their capacity in forming biopolymeric films, being biocompatible and non-toxic; however, its hydrophilicity poses a challenge. Essential oils, rich in bioactives, attract research interest aiming to enhance the protective barrier of films and enable their application in packaging. This study produced films based on cross-linked Nile tilapia skin gelatin, incorporating garlic essential oil. Gelatin obtained through partial collagen hydrolysis from the fish skin and cross-linked with gallic acid had hydroxyproline content of 10.02 g 100 g-1 and gel strength of 287 g, which were consistent with other studies. Oil extraction used supercritical CO2 as a solvent and ethanol as a cosolvent, following a factorial experimental design, evaluating the extraction temperature (40 °C and 70 °C) and cosolvent ratio (1:1 and 1:3), with three central points. Extraction was successful, with higher yields on a dry basis at 70 °C (88.35 %), using a 1:1 cosolvent ratio. Films incorporated with oil exhibited lower water vapor permeability (WVP) than those with only cross-linked gelatin (1.59 (g m-1 s-1 Pa-1) 1011). The film with the most suitable tensile strength (19.07 MPa), elongation (120.91 %), and WVP (1.09 (g m-1 s-1 Pa-1) 1011) properties contained garlic oil extracted at the central point (55 °C and 1:2). Thermal analysis indicated increased melting temperatures in films with added oil, suggesting low thermal degradation. These results suggest that garlic oil addition can improve the properties of fish gelatin-based films, making them promising for biodegradable packaging.


Subject(s)
Food Packaging , Garlic , Gelatin , Oils, Volatile , Permeability , Gelatin/chemistry , Oils, Volatile/chemistry , Animals , Garlic/chemistry , Food Packaging/methods , Tensile Strength , Steam , Sulfides/chemistry , Hydrophobic and Hydrophilic Interactions , Skin/chemistry
3.
Food Res Int ; 188: 114453, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823833

ABSTRACT

In this study, whipped cream with blends of micellar casein (MCN) and whey protein (WPI) in different ratios were prepared to investigate the role of protein interfacial behavior in determining foam properties at multiple scales, using theoretical modeling, and microscopic and macroscopic analysis. Fluid force microscopy has been used for the first time as a more realistic and direct means of analyzing interfaces properties in multiphase systems. The adsorption kinetics showed that the interfacial permeability constant of WPI (4.24 × 10-4 s-1) was significantly higher than that of the MCN (2.97 × 10-4 s-1), and the WPI interfacial layer had a higher modulus of elasticity (71.38 mN/m) than that of the MCN (47.89 mN/m). This model was validated via the mechanical analysis of the fat globules in real emulsions. The WPI-stabilized fat globule was found to have a higher Young's modulus (219.67 Pa), which contributes to the integrity of its fat globule morphology. As the ratio of MCN was increased in the sample, however, both the interfacial modulus and Young's modulus decreased. Moreover, the rate of partial coalescence was found to increase, a phenomenon that decreased the stability of the emulsion and increased the rate of aeration. The mechanical analysis also revealed a higher level of adhesion between MCN-stabilized fat globule (25.16 nN), which increased fat globule aggregation and emulsion viscosity, while improving thixotropic recovery. The synergistic effect of the blended MCN and WPI provided the highest overrun, at 194.53 %. These studies elucidate the role of the interfacial behavior of proteins in determining the quality of whipped cream and provide ideas for the application of proteins in multiphase systems.


Subject(s)
Caseins , Micelles , Whey Proteins , Whey Proteins/chemistry , Caseins/chemistry , Emulsions/chemistry , Dairy Products , Lipid Droplets/chemistry , Adsorption , Kinetics , Permeability , Food Handling/methods , Glycolipids/chemistry , Elastic Modulus , Viscosity , Glycoproteins
4.
Food Res Int ; 188: 114475, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823838

ABSTRACT

This work aimed to develop edible emulsion-based barriers in the form of chitosan composite films, with a focus on assessing the impacts of carnauba wax, rosin resin, and zinc oxide nanoparticles on their properties. Six films were produced by casting using chitosan as polymer base and glycerol as plasticizer. Acetic acid and polysorbate 80 were also used to facilitate the dissolution and mixing of the components. The six filmogenic solutions contained chitosan at 1.2% w/v, wax or resin content with 0 or 0.6% m/v and ZnO with 0 or 0.05% m/v. The dried films were characterized according to their chemical, barrier, mechanical, thermal and optical properties. All treatments resulted in flexible films. Chitosan films appeared smoother and more uniform under SEM imaging, while carnauba wax films displayed roughness due to their hydrophobic nature. Wax and resin films were less transparent and water soluble than the chitosan-only films. On the other hand, the addition of ZnO in the formulations increased the solubility of the films. The sorption degree was in line with the solubility results, i.e., films with ZnO presented higher sorption degree and solubility values. All treatments showed low or non-light UV transmission, indicating that the films provide good barrier to UV light. In the visible light region, films of resin with ZnO showed the lowest transmittance values, hence offering a good barrier to visible light. Among the evaluated films, chitosan, and resin films with ZnO nanoparticles were more rigid and resistant to deformation. Overall, films produced with rosin resin and ZnO nanoparticles showed potential improvements in barrier, mechanical, thermal, and optical properties, mainly due to their low water solubility, good UV protection and low permeability to water vapor and oxygen, which are suitable for using in formulations, intended to produce edible films and coatings.


Subject(s)
Chitosan , Nanocomposites , Resins, Plant , Solubility , Waxes , Zinc Oxide , Chitosan/chemistry , Zinc Oxide/chemistry , Nanocomposites/chemistry , Resins, Plant/chemistry , Waxes/chemistry , Nanoparticles/chemistry , Food Packaging/methods , Permeability
5.
Food Res Int ; 188: 114502, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823845

ABSTRACT

Lycium barbarum L. berries have a remarkable chemical composition and extensive biological activities, being a valuable component of health and nutraceutical practices. Nevertheless, a deep insight on the intestinal permeation of the pro-healthy bioactive compounds is urgently needed to predict the real effects on human body. This study attempted, for the first time, to optimize the Ultrasound-Assisted Extraction (UAE) of goji berries using a Response Surface Methodology approach and establish the intestinal permeation of the principal pro-healthy compounds. The optimal extraction conditions were a solid:liquid ratio of 8.75 % for 56.21 min, using an intensity of 59.05 W/m2. The optimal extract displayed a remarkable antioxidant capacity, with LC/DAD-ESI-MS analysis unveiled a diverse phytochemical profile, encompassing different compounds (e.g. glu-lycibarbarspermidine F, 2-glu-kukoamine, rutin, 3,5-dicaffeoylquinic acid). The intestinal co-culture model demonstrated that glu-lycibarbarspermidine F (isomer 2) (73.70 %), 3,5-dicaffeoylquinic acid (52.66 %), and isorhamnetin-3-O-rutinoside (49.31 %) traversed the intestinal cell layer, exerting beneficial health-promoting effects.


Subject(s)
Antioxidants , Fruit , Lycium , Plant Extracts , Lycium/chemistry , Fruit/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Antioxidants/pharmacology , Antioxidants/isolation & purification , Humans , Permeability , Ultrasonic Waves , Phytochemicals/isolation & purification , Intestinal Mucosa/metabolism , Caco-2 Cells , Intestinal Absorption , Rutin/isolation & purification , Ultrasonics/methods , Intestinal Barrier Function
6.
J Toxicol Sci ; 49(5): 219-230, 2024.
Article in English | MEDLINE | ID: mdl-38692909

ABSTRACT

Quantitative structure permeation relationship (QSPR) models have gained prominence in recent years owing to their capacity to elucidate the influence of physicochemical properties on the dermal absorption of chemicals. These models facilitate the prediction of permeation coefficient (Kp) values, indicating the skin permeability of a chemical under infinite dose conditions. Conversely, obtaining dermal absorption rates (DAs) under finite dose conditions, which are crucial for skin product safety evaluation, remains a challenge when relying solely on Kp predictions from QSPR models. One proposed resolution involves using Kroes' methodology, categorizing DAs based on Kp values; however, refinement becomes necessary owing to discreteness in the obtained values. We previously developed a mathematical model using Kp values obtained from in vitro dermal absorption tests to predict DAs. The present study introduces a new methodology, Integrating Mathematical Approaches (IMAS), which combines QSPR models and our mathematical model to predict DAs for risk assessments without conducting in vitro dermal absorption tests. Regarding 40 chemicals (76.1 ≤ MW ≤ 220; -1.4 ≤ Log Ko/w ≤ 3.1), IMAS showed that 65.0% (26/40) predictions of DA values were accurate to within twofold of the observed values in finite dose experiments. Compared to Kroes' methodology, IMAS notably mitigated overestimation, particularly for hydrophilic chemicals with water solubility exceeding 57.0 mg/cm3. These findings highlight the value of IMAS as a tool for skin product risk assessments, particularly for hydrophilic compounds.


Subject(s)
Permeability , Quantitative Structure-Activity Relationship , Skin Absorption , Risk Assessment , Skin/metabolism , Humans , Models, Theoretical , Solubility , Hydrophobic and Hydrophilic Interactions , Animals , Models, Biological
7.
Methods Mol Biol ; 2799: 177-200, 2024.
Article in English | MEDLINE | ID: mdl-38727908

ABSTRACT

In the mammalian central nervous system (CNS), fast excitatory transmission relies primarily on the ionic fluxes generated by ionotropic glutamate receptors (iGluRs). Among iGluRs, NMDA receptors (NMDARs) are unique in their ability to pass large, Ca2+-rich currents. Importantly, their high Ca2+ permeability is essential for normal CNS function and is under physiological control. For this reason, the accurate measurement of NMDA receptor Ca2+ permeability represents a valuable experimental step in evaluating the mechanism by which these receptors contribute to a variety of physiological and pathological conditions. In this chapter, we provide a theoretical and practical overview of the common methods used to estimate the Ca2+ permeability of ion channels as they apply to NMDA receptors. Specifically, we describe the principles and methodology used to calculate relative permeability (PCa/PNa) and fractional permeability (Pf), along with the relationship between these two metrics. With increasing knowledge about the structural dynamics of ion channels and of the ongoing environmental fluctuations in which channels operate in vivo, the ability to quantify the Ca2+ entering cells through specific ion channels remains a tool essential to delineating the molecular mechanisms that support health and cause disease.


Subject(s)
Calcium , Patch-Clamp Techniques , Receptors, N-Methyl-D-Aspartate , Receptors, N-Methyl-D-Aspartate/metabolism , Calcium/metabolism , Patch-Clamp Techniques/methods , Animals , Humans , Permeability , Cell Membrane Permeability
8.
J Med Chem ; 67(9): 7470-7486, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38690769

ABSTRACT

We assessed factors that determine the tissue-specific bioactivation of ProTide prodrugs by comparing the disposition and activation of remdesivir (RDV), its methylpropyl and isopropyl ester analogues (MeRDV and IsoRDV, respectively), the oral prodrug GS-621763, and the parent nucleotide GS-441524 (Nuc). RDV and MeRDV yielded more active metabolite remdesivir-triphosphate (RDV-TP) than IsoRDV, GS-621763, and Nuc in human lung cell models due to superior cell permeability and higher susceptivity to cathepsin A. Intravenous administration to mice showed that RDV and MeRDV delivered significantly more RDV-TP to the lung than other compounds. Nevertheless, all four ester prodrugs exhibited very low oral bioavailability (<2%), with Nuc being the predominant metabolite in blood. In conclusion, ProTides prodrugs, such as RDV and MeRDV, are more efficient in delivering active metabolites to the lung than Nuc, driven by high cell permeability and susceptivity to cathepsin A. Optimizing ProTides' ester structures is an effective strategy for enhancing prodrug activation in the lung.


Subject(s)
Adenosine/analogs & derivatives , Antiviral Agents , Cathepsin A , Lung , Prodrugs , Prodrugs/chemistry , Prodrugs/metabolism , Prodrugs/pharmacokinetics , Prodrugs/pharmacology , Animals , Mice , Antiviral Agents/pharmacokinetics , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/metabolism , Humans , Cathepsin A/metabolism , Lung/metabolism , Cell Membrane Permeability/drug effects , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacokinetics , Adenosine Monophosphate/metabolism , Adenosine Monophosphate/chemistry , Adenosine Monophosphate/pharmacology , Alanine/analogs & derivatives , Alanine/chemistry , Alanine/pharmacokinetics , Alanine/metabolism , Alanine/pharmacology , Permeability , ProTides
9.
Sci Rep ; 14(1): 10193, 2024 05 03.
Article in English | MEDLINE | ID: mdl-38702361

ABSTRACT

Amphibians are often recognized as bioindicators of healthy ecosystems. The persistence of amphibian populations in heavily contaminated environments provides an excellent opportunity to investigate rapid vertebrate adaptations to harmful contaminants. Using a combination of culture-based challenge assays and a skin permeability assay, we tested whether the skin-associated microbiota may confer adaptive tolerance to tropical amphibians in regions heavily contaminated with arsenic, thus supporting the adaptive microbiome principle and immune interactions of the amphibian mucus. At lower arsenic concentrations (1 and 5 mM As3+), we found a significantly higher number of bacterial isolates tolerant to arsenic from amphibians sampled at an arsenic contaminated region (TES) than from amphibians sampled at an arsenic free region (JN). Strikingly, none of the bacterial isolates from our arsenic free region tolerated high concentrations of arsenic. In our skin permeability experiment, where we tested whether a subset of arsenic-tolerant bacterial isolates could reduce skin permeability to arsenic, we found that isolates known to tolerate high concentrations of arsenic significantly reduced amphibian skin permeability to this metalloid. This pattern did not hold true for bacterial isolates with low arsenic tolerance. Our results describe a pattern of environmental selection of arsenic-tolerant skin bacteria capable of protecting amphibians from intoxication, which helps explain the persistence of amphibian populations in water bodies heavily contaminated with arsenic.


Subject(s)
Amphibians , Arsenic , Microbiota , Skin , Animals , Arsenic/metabolism , Arsenic/toxicity , Microbiota/drug effects , Skin/microbiology , Skin/drug effects , Skin/metabolism , Amphibians/microbiology , Bacteria/drug effects , Bacteria/classification , Bacteria/metabolism , Bacteria/genetics , Permeability/drug effects
10.
Food Res Int ; 186: 114338, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38729719

ABSTRACT

Women with the extremely prevalent polycystic ovary syndromegather multiple cardiovascular risk factors and chronic subclinical inflammation. Interactions between diet, adiposity, and gut microbiota modulate intestinal permeabilityand bacterial product translocation, and may contribute to the chronic inflammation process associated with the polycystic ovary syndrome. In the present study, we aimed to address the effects of obesity, functional hyperandrogenism, and diverse oral macronutrients on intestinal permeabilityby measuring circulating markers of gut barrier dysfunction and endotoxemia. Participants included 17 non-hyperandrogenic control women, 17 women with polycystic ovary syndrome, and 19 men that were submitted to glucose, lipid, and protein oral loads. Lipopolysaccharide-binding protein, plasma soluble CD14, succinate, zonulin family peptide, and glucagon-like peptide-2 were determined at fasting and after oral challenges. Macronutrient challenges induced diverse changes on circulating intestinal permeabilitybiomarkers in the acute postprancial period, with lipids and proteins showing the most unfavorable and favorable effects, respectively. Particularly, lipopolysaccharide-binding protein, zonulin family peptide, and glucagon-like peptide-2 responses were deregulated by the presence of obesity after glucose and lipid challenges. Obese subjects showed higher fasting intestinal permeabilitybiomarkers levels than non-obese individuals, except for plasma soluble CD14. The polycystic ovary syndromeexacerbated the effect of obesity further increasing fasting glucagon-like peptide-2, lipopolysaccharide-binding protein, and succinate concentrations. We observed specific interactions of the polycystic ovary syndromewith obesity in the postprandial response of succinate, zonulin family peptide, and glucagon-like peptide-2. In summary, obesity and polycystic ovary syndromemodify the effect of diverse macronutrients on the gut barrier, and alsoinfluence intestinal permeabilityat fasting,contributing to the morbidity of functional hyperandrogenism by inducing endotoxemia and subclinical chronic inflammation.


Subject(s)
Fasting , Glucagon-Like Peptide 2 , Obesity , Permeability , Polycystic Ovary Syndrome , Humans , Polycystic Ovary Syndrome/metabolism , Female , Adult , Fasting/blood , Male , Glucagon-Like Peptide 2/blood , Intestinal Mucosa/metabolism , Gastrointestinal Microbiome , Nutrients , Young Adult , Haptoglobins/metabolism , Endotoxemia , Lipopolysaccharide Receptors/blood , Acute-Phase Proteins/metabolism , Biomarkers/blood , Membrane Glycoproteins/blood , Membrane Glycoproteins/metabolism , Dietary Fats , Glucose/metabolism , Intestinal Barrier Function , Carrier Proteins , Protein Precursors
11.
Viruses ; 16(5)2024 05 15.
Article in English | MEDLINE | ID: mdl-38793666

ABSTRACT

SARS-CoV-2 primarily infects the lungs via the ACE2 receptor but also other organs including the kidneys, the gastrointestinal tract, the heart, and the skin. SARS-CoV-2 also infects the brain, but the hematogenous route of viral entry to the brain is still not fully characterized. Understanding how SARS-CoV-2 traverses the blood-brain barrier (BBB) as well as how it affects the molecular functions of the BBB are unclear. In this study, we investigated the roles of the receptors ACE2 and DPP4 in the SARS-CoV-2 infection of the discrete cellular components of a transwell BBB model comprising HUVECs, astrocytes, and pericytes. Our results demonstrate that direct infection on the BBB model does not modulate paracellular permeability. Also, our results show that SARS-CoV-2 utilizes clathrin and caveolin-mediated endocytosis to traverse the BBB, resulting in the direct infection of the brain side of the BBB model with a minimal endothelial infection. In conclusion, the BBB is susceptible to SARS-CoV-2 infection in multiple ways, including the direct infection of endothelium, astrocytes, and pericytes involving ACE2 and/or DPP4 and the blood-to-brain transcytosis, which is an event that does not require the presence of host receptors.


Subject(s)
Angiotensin-Converting Enzyme 2 , Astrocytes , Blood-Brain Barrier , COVID-19 , Dipeptidyl Peptidase 4 , Pericytes , SARS-CoV-2 , Transcytosis , Virus Internalization , Blood-Brain Barrier/virology , Blood-Brain Barrier/metabolism , Humans , SARS-CoV-2/physiology , Angiotensin-Converting Enzyme 2/metabolism , Pericytes/virology , Pericytes/metabolism , COVID-19/virology , COVID-19/metabolism , Astrocytes/virology , Astrocytes/metabolism , Dipeptidyl Peptidase 4/metabolism , Brain/virology , Brain/metabolism , Endocytosis , Human Umbilical Vein Endothelial Cells/virology , Permeability
12.
Water Environ Res ; 96(5): e11018, 2024 May.
Article in English | MEDLINE | ID: mdl-38712584

ABSTRACT

Applicable and low-cost ultrafiltration membranes based on waste polystyrene (WPS) blend and poly vinylidene fluoride (PVDF) were effectively cast on nonwoven support using phase inversion method. Analysis was done into how the WPS ratio affected the morphology and antifouling performance of the fabricated membranes. Cross flow filtration of pure water and various types of polluted aqueous solutions as the feed was used to assess the performance of the membranes. The morphology analysis shows that the WPS/PVDF membrane layer has completely changed from a spongy structure to a finger-like structure. In addition, the modified membrane with 50% WPS demonstrated that the trade-off between selectivity and permeability is met by a significant improvement in the rejection of the membrane with a reduction in permeate flux due to the addition of PVDF. With a water permeability of 50 LMH and 44 LMH, respectively, the optimized WPS-PVDF membrane with 50% WPS could reject 81% and 74% of Congo red dye (CR) and methylene blue dye (MB), respectively. The flux recovery ratio (FRR) reached to 88.2% by increasing PVDF concentration with 50% wt. Also, this membrane has the lowest irreversible fouling (Rir) value of 11.7% and lowest reversible fouling (Rr) value of 27.9%. The percent of cleaning efficiency reach to 71%, 90%, and 85% after eight cycles of humic acid (HA), CR, and MB filtration, respectively, for the modified PS-PVDF (50%-50%). However, higher PVDF values cause the membrane's pores to become clogged, increase the irreversible fouling, and decrease the cleaning efficiency. In addition to providing promising filtration results, the modified membrane is inexpensive because it was made from waste polystyrene, and as a result, it could be scaled up to treat colored wastewater produced by textile industries. PRACTITIONER POINTS: Recycling of plastic waste as an UF membrane for water/wastewater treatment was successfully prepared and investigated. Mechanical properties showed reasonable response with adding PVDF. The modified membrane with 50% PS demonstrated that the trade-off between selectivity and permeability is met by a significant improvement in the rejection.


Subject(s)
Coloring Agents , Fluorocarbon Polymers , Membranes, Artificial , Ultrafiltration , Water Pollutants, Chemical , Water Purification , Ultrafiltration/methods , Coloring Agents/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/isolation & purification , Water Purification/methods , Plastics/chemistry , Waste Disposal, Fluid/methods , Polyvinyls/chemistry , Permeability
13.
AAPS PharmSciTech ; 25(5): 112, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38744715

ABSTRACT

This study aimed to develop a propellant-free topical spray formulation of Etodolac (BCS-II), a potent NSAID, which could be beneficial in the medical field for the effective treatment of pain and inflammation conditions. The developed novel propellant-free spray formulation is user-friendly, cost-effective, propellant-free, eco-friendly, enhances the penetration of Etodolac through the skin, and has a quick onset of action. Various formulations were developed by adjusting the concentrations of different components, including lecithin, buffering agents, film-forming agents, plasticizers, and permeation enhancers. The prepared propellant-free spray formulations were then extensively characterized and evaluated through various in vitro, ex vivo, and in vivo parameters. The optimized formulation exhibits an average shot weight of 0.24 ± 0.30 ml and an average drug content or content uniformity of 87.3 ± 1.01% per spray. Additionally, the optimized formulation exhibits an evaporation time of 3 ± 0.24 min. The skin permeation study demonstrated that the permeability coefficients of the optimized spray formulation were 21.42 cm/h for rat skin, 13.64 cm/h for mice skin, and 18.97 cm/h for the Strat-M membrane. When assessing its potential for drug deposition using rat skin, mice skin, and the Strat-M membrane, the enhancement ratios for the optimized formulation were 1.88, 2.46, and 1.92, respectively against pure drug solution. The findings from our study suggest that the propellant-free Etodolac spray is a reliable and safe topical formulation. It demonstrates enhanced skin deposition, and improved effectiveness, and is free from any skin irritation concerns.


Subject(s)
Administration, Cutaneous , Etodolac , Skin Absorption , Skin , Animals , Etodolac/administration & dosage , Etodolac/pharmacokinetics , Etodolac/chemistry , Rats , Mice , Skin Absorption/physiology , Skin/metabolism , Skin/drug effects , Male , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Acute Pain/drug therapy , Chemistry, Pharmaceutical/methods , Permeability , Rats, Sprague-Dawley , Drug Compounding/methods
14.
Biol Pharm Bull ; 47(5): 997-999, 2024.
Article in English | MEDLINE | ID: mdl-38777759

ABSTRACT

Patch tests are often used in safety evaluations to identify the substance causing skin irritation, but the same substance can sometimes give positive or negative results depending on the test conditions. Here, we investigated differences in the skin penetration of two test compounds under different application conditions. We studied the effects of the anionic surfactant sodium dodecyl sulfate (SDS) and the nonionic surfactant polysorbate 80 (PS) on skin penetration of the preservatives methylisothiazolinone (MT) and methylchloroisothiazolinone (MCT), which are used in cosmetics such as shampoos. The skin permeation of MT was enhanced by SDS but was unchanged by PS. Skin impedance decreased in the presence of SDS whereas PS had the same effect as the control aqueous solution, suggesting that SDS reduction of the barrier function of skin affects the permeation of MT, a hydrophilic drug. Application of a mixture of MCT and MT in the presence of SDS did not affect the skin permeation of MCT whereas the permeation of MT was enhanced by SDS, indicating that the skin permeation of MCT is less affected by SDS than is MT. Thus, attention should be paid to the possible effect of co-solutes, especially hydrophilic drugs.


Subject(s)
Polysorbates , Skin Absorption , Skin , Sodium Dodecyl Sulfate , Surface-Active Agents , Thiazoles , Thiazoles/pharmacokinetics , Surface-Active Agents/pharmacology , Skin Absorption/drug effects , Polysorbates/pharmacology , Skin/metabolism , Skin/drug effects , Animals , Preservatives, Pharmaceutical , Swine , Cosmetics/pharmacokinetics , Electric Impedance , Permeability/drug effects
15.
Physiol Rep ; 12(10): e16087, 2024 May.
Article in English | MEDLINE | ID: mdl-38783385

ABSTRACT

Strenuous exercise can result in disruption of intestinal barrier function and occurrence of gastrointestinal symptoms. The aim of this exploratory study was to elucidate systemic effects of increased intestinal permeability after high-intensity exercise. Forty-one endurance-trained subjects performed a 60-min treadmill run at 80% VO2max. Small intestinal permeability was measured as urinary excretion ratio of lactulose/rhamnose (L/R). Blood, saliva and feces were analyzed for gut barrier and immune-related biomarkers. The exercise challenge increased several markers of intestinal barrier disruption, immune function and oxidative stress. We found a negative correlation between L/R ratio and uric acid (r = -0.480), as well as a positive correlation between the L/R ratio and fecal chromogranin A in male participants (r = 0.555). No significant correlations were found between any of the markers and gastrointestinal symptoms, however, perceived exertion correlated with the combination of IL-6, IL-10 and salivary cortisol (r = 0.492). The lack of correlation between intestinal permeability and gastrointestinal symptoms could be due to minor symptoms experienced in lab settings compared to real-life competitions. The correlation between L/R ratio and uric acid might imply a barrier-protective effect of uric acid, and inflammatory processes due to strenuous exercise seem to play an important role regarding physical exhaustion.


Subject(s)
Biomarkers , Exercise , Humans , Male , Adult , Biomarkers/blood , Biomarkers/metabolism , Exercise/physiology , Female , Intestinal Mucosa/metabolism , Uric Acid/blood , Uric Acid/metabolism , Permeability , Lactulose/urine , Lactulose/metabolism , Rhamnose/metabolism , Young Adult , Oxidative Stress , Chromogranin A/metabolism , Hydrocortisone/blood , Hydrocortisone/metabolism , Saliva/metabolism
16.
J Chem Inf Model ; 64(10): 4298-4309, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38700741

ABSTRACT

The intricate nature of the blood-brain barrier (BBB) poses a significant challenge in predicting drug permeability, which is crucial for assessing central nervous system (CNS) drug efficacy and safety. This research utilizes an innovative approach, the classification read-across structure-activity relationship (c-RASAR) framework, that leverages machine learning (ML) to enhance the accuracy of BBB permeability predictions. The c-RASAR framework seamlessly integrates principles from both read-across and QSAR methodologies, underscoring the need to consider similarity-related aspects during the development of the c-RASAR model. It is crucial to note that the primary goal of this research is not to introduce yet another model for predicting BBB permeability but rather to showcase the refinement in predicting the BBB permeability of organic compounds through the introduction of a c-RASAR approach. This groundbreaking methodology aims to elevate the accuracy of assessing neuropharmacological implications and streamline the process of drug development. In this study, an ML-based c-RASAR linear discriminant analysis (LDA) model was developed using a dataset of 7807 compounds, encompassing both BBB-permeable and -nonpermeable substances sourced from the B3DB database (freely accessible from https://github.com/theochem/B3DB), for predicting BBB permeability in lead discovery for CNS drugs. The model's predictive capability was then validated using three external sets: one containing 276,518 natural products (NPs) from the LOTUS database (accessible from https://lotus.naturalproducts.net/download) for data gap filling, another comprising 13,002 drug-like/drug compounds from the DrugBank database (available from https://go.drugbank.com/), and a third set of 56 FDA-approved drugs to assess the model's reliability. Further diversifying the predictive arsenal, various other ML-based c-RASAR models were also developed for comparison purposes. The proposed c-RASAR framework emerged as a powerful tool for predicting BBB permeability. This research not only advances the understanding of molecular determinants influencing CNS drug permeability but also provides a versatile computational platform for the rapid assessment of diverse compounds, facilitating informed decision-making in drug development and design.


Subject(s)
Blood-Brain Barrier , Machine Learning , Permeability , Quantitative Structure-Activity Relationship , Blood-Brain Barrier/metabolism , Humans , Discriminant Analysis
19.
Chem Rev ; 124(10): 6543-6591, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38728658

ABSTRACT

Bioelectronics integrates electronics with biological organs, sustaining the natural functions of the organs. Organs dynamically interact with the external environment, managing internal equilibrium and responding to external stimuli. These interactions are crucial for maintaining homeostasis. Additionally, biological organs possess a soft and stretchable nature; encountering objects with differing properties can disrupt their function. Therefore, when electronic devices come into contact with biological objects, the permeability of these devices, enabling interactions and substance exchanges with the external environment, and the mechanical compliance are crucial for maintaining the inherent functionality of biological organs. This review discusses recent advancements in soft and permeable bioelectronics, emphasizing materials, structures, and a wide range of applications. The review also addresses current challenges and potential solutions, providing insights into the integration of electronics with biological organs.


Subject(s)
Electronics , Humans , Permeability , Wearable Electronic Devices , Animals
20.
J Transl Med ; 22(1): 488, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773576

ABSTRACT

Ulcerative colitis (UC) is an idiopathic, chronic inflammatory condition of the colon, characterized by repeated attacks, a lack of effective treatment options, and significant physical and mental health complications for patients. The endoplasmic reticulum (ER) is a vital intracellular organelle in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is induced when the body is exposed to adverse external stimuli. Numerous studies have shown that ERS-induced apoptosis plays a vital role in the pathogenesis of UC. Mogroside V (MV), an active ingredient of Monk fruit, has demonstrated excellent anti-inflammatory and antioxidant effects. In this study, we investigated the therapeutic effects of MV on dextran sulfate sodium (DSS)-induced UC and its potential mechanisms based on ERS. The results showed that MV exerted a protective effect against DSS-induced UC in mice as reflected by reduced DAI scores, increased colon length, reduced histological scores of the colon, and levels of pro-inflammatory cytokines, as well as decreased intestinal permeability. In addition, the expression of ERS pathway including BIP, PERK, eIF2α, ATF4, CHOP, as well as the apoptosis-related protein including Caspase-12, Bcl-2 and Bax, was found to be elevated in UC. However, MV treatment significantly inhibited the UC and reversed the expression of inflammation signaling pathway including ERS and ERS-induced apoptosis. Additionally, the addition of tunicamycin (Tm), an ERS activator, significantly weakened the therapeutic effect of MV on UC in mice. These findings suggest that MV may be a therapeutic agent for the treatment of DSS-induced UC by inhibiting the activation of the ERS-apoptosis pathway, and may provide a novel avenue for the treatment of UC.


Subject(s)
Apoptosis , Colitis, Ulcerative , Dextran Sulfate , Endoplasmic Reticulum Stress , Animals , Endoplasmic Reticulum Stress/drug effects , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/metabolism , Apoptosis/drug effects , Male , Mice, Inbred C57BL , Colon/pathology , Colon/drug effects , Triterpenes/pharmacology , Triterpenes/therapeutic use , Mice , Cytokines/metabolism , Permeability/drug effects , Signal Transduction/drug effects
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