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In July 2018, the Food and Drug Administration warned about a possible relationship between dilated cardiomyopathy (DCM) in dogs and the consumption of dog food formulated with potatoes and pulse ingredients. This issue may impede utilization of pulse ingredients in dog food or consideration of alternative proteins. Pulse ingredients have been used in the pet food industry for over 2 decades and represent a valuable source of protein to compliment animal-based ingredients. Moreover, individual ingredients used in commercial foods do not represent the final nutrient concentration of the complete diet. Thus, nutritionists formulating dog food must balance complementary ingredients to fulfill the animal's nutrient needs in the final diet. There are multiple factors that should be considered, including differences in nutrient digestibility and overall bioavailability, the fermentability and quantity of fiber, and interactions among food constituents that can increase the risk of DCM development. Taurine is a dispensable amino acid that has been linked to DCM in dogs. As such, adequate supply of taurine and/or precursors for taurine synthesis plays an important role in preventing DCM. However, requirements of amino acids in dogs are not well investigated and are presented in total dietary content basis which does not account for bioavailability or digestibility. Similarly, any nutrient (e.g., soluble and fermentable fiber) or physiological condition (e.g., size of the dog, sex, and age) that increases the requirement for taurine will also augment the possibility for DCM development. Dog food formulators should have a deep knowledge of processing methodologies and nutrient interactions beyond meeting the Association of American Feed Control Officials nutrient profiles and should not carelessly follow unsubstantiated market trends. Vegetable ingredients, including pulses, are nutritious and can be used in combination with complementary ingredients to meet the nutritional needs of the dog.

Background: Cereals are the most staple foods in human diet and the main components of the daily diet. This work was designed to determine the level of essential and non-essential elements, the in vitro bioavailability, interrelationship, and associated health risk in consumed cereal grains in Nigeria to assess their safety and wholesomeness. Methods: The contents of phytate, oxalate, and some major-, trace- and potentially toxic elements were determined in 36 samples of barley, maize, millet, rice, sorghum, and wheat marketed in Nigeria. Results: The data showed variable significant (p

Wildfires are expected to become more frequent and intensive at the global scale due to climate change. Many studies have focused on the loss of mercury (Hg) from burned forests; however, little is known about the origins, concentration, reactivity, and bioavailability of Hg in residual ash materials in postfire landscapes. We examine Hg levels and reactivity in black ash (BA, low burn intensity) and white ash (WA, high burn intensity) generated from two recent northern California wildfires and document that all ash samples contained measurable, but highly variable, Hg levels ranging from 4 to 125 ng/g dry wt. ( n = 28). Stable Hg isotopic compositions measured in select ash samples suggest that most Hg in wildfire ash is derived from vegetation. Ash samples had a highly variable fraction of Hg in recalcitrant forms (0-75%), and this recalcitrant Hg pool appears to be associated with the black carbon fraction in ash. Both BA and WA were found to strongly sequester aqueous inorganic Hg but not gaseous elemental Hg under controlled conditions. During anoxic ash incubation with natural surface water, we find that Hg in most ash samples had a minimal release and low methylation potential. Thus, the formation of wildfire ash can sequester Hg into relatively nonbioavailable forms, attenuating the potentially adverse effects of Hg erosion and transport to aquatic environments along with eroded wildfire ash.

To address the limited bioavailability and intolerance of the conventional itraconazole (ITZ) formulations, a new formulation labeled super bioavailability (SUBA) itraconazole has been developed; however, the specific effects of food and gastric pH are unknown. This study evaluated the pharmacokinetic profile of SUBA itraconazole under fasting and fed conditions, as well as with the concomitant administration of a proton pump inhibitor. First, the effect of food was assessed in an open-label, randomized, crossover bioavailability study of 65-mg SUBA itraconazole capsules (2 65-mg capsules twice a day) in healthy adults (n = 20) under fasting and fed conditions to steady-state levels. Second, an open-label, two-treatment, fixed-sequence comparative bioavailability study in healthy adults (n = 28) under fasted conditions compared the pharmacokinetics of a single oral dose of SUBA itraconazole capsules (2 65-mg capsules/day) with and without coadministration of daily omeprazole delayed-release capsules (1 40-mg capsule/day) under steady-state conditions. In the fed and fasted states, SUBA itraconazole demonstrated similar concentrations at the end of the dosing interval, with modestly lower total and peak ITZ exposure being shown when it was administered under fed conditions than when it was administered in the fasted state, with fed state/fasted state ratios of 78.09% (90% confidence interval [CI], 74.49 to 81.86%) for the area under the concentration-time curve over the dosing interval (14,183.2 versus 18,479.8 ng · h/ml), 73.05% (90% CI, 69.01 to 77.33%) for the maximum concentration at steady state (1,519.1 versus 2,085.2 ng/ml), and 91.53% (90% CI, 86.41 to 96.96%) for the trough concentration (1,071.5 versus 1,218.5 ng/ml) being found. When dosed concomitantly with omeprazole, there was a 22% increase in the total plasma exposure of ITZ, as measured by the area under the concentration-time curve from time zero to infinity (P = 0.0069), and a 31% increase in the peak plasma exposure of ITZ, as measured by the maximum concentration (P = 0.0083).

Lopinavir/ritonavir (LPV/r) is recommended by the World Health Organization as first-line treatment for HIV-infected infants and young children. We performed a composite population pharmacokinetic (PK) analysis on LPV plasma concentration data from 6 pediatric and adult studies to determine maturation and formulation effects from infancy to adulthood. Intensive PK data were available for infants, children, adolescents, and adults (297 intensive profiles/1662 LPV concentrations). LPV PK data included 1 adult, 1 combined pediatric-adult, and 4 pediatric studies (age 6 weeks to 63 years) with 3 formulations (gel-capsule, liquid, melt-extrusion tablets). LPV concentrations were modeled using nonlinear mixed effects modeling (NONMEM v. 7.3; GloboMax, Hanover, Maryland) with a one compartment semiphysiologic model. LPV clearance was described by hepatic plasma flow (QHP ) times hepatic extraction (EH ), with EH estimated from the PK data. Volume was scaled by linear weight (WT/70)1.0 . Bioavailability was assessed separately as a function of hepatic extraction and the fraction absorbed from the gastrointestinal tract. The absorption component of bioavailability increased with age and tablet formulation. Monte Carlo simulations of the final model using current World Health Organization weight-band dosing recommendations demonstrated that participants younger than 6 months of age had a lower area under the drug concentration-time curve (94.8 vs >107.4 μg hr/mL) and minimum observed concentration of drug in blood plasma (5.0 vs > 7.1 μg/mL) values compared to older children and adults. Although World Health Organization dosing recommendations include a larger dosage (mg/m2 ) in infants to account for higher apparent clearance, they still result in low LPV concentrations in many infants younger than 6 months of age receiving the liquid formulation.

Background parenchymal enhancement (BPE) is the degree to which normal breast tissue enhances on contrast-enhanced magnetic resonance imaging (MRI). MRI-density is a volumetric measure of breast density that is highly correlated with mammographic density, an established breast cancer risk factor. Endogenous estrogen concentrations are positively associated with postmenopausal breast cancer risk and BPE has been shown to be sensitive to hormonal exposures. The objective of our study was to examine the relationship between BPE and MRI-density and serum hormone concentrations in postmenopausal women. This was a study of cancer-free postmenopausal women undergoing contrast-enhanced breast MRI (N = 118). At the time of MRI all women completed a self-administered questionnaire and blood samples were collected for hormone analyses. Serum concentrations of estrone (E1), estradiol (E2) and bioavailable E2 were examined by category of BPE and MRI-density. Compared to women with minimal BPE, those who had marked BPE had significantly higher serum concentrations of E1, E2 and bioavailable E2 (90% increase, ptrend across all categories = 0.001; 150% increase, ptrend  = 0.001; and 158% increase, ptrend  = 0.001, respectively). These associations were only affected to a minor extent by adjustment for BMI and other variables. After adjustment for BMI, no significant associations between MRI-density and serum E1, E2 and bioavailable E2 were observed. Serum estrogen concentrations were significantly positively associated with BPE. Our study provides further evidence of the hormone-sensitive nature of BPE, indicating a potential role for BPE as an imaging marker of endogenous and exogenous hormonal exposures in the breast.

In grafted plants, rootstocks assure the mineral nutrition of the scion and modify its development. In this study, we show that two grapevine rootstock genotypes have different shoot branching architectures when cultivated as cuttings and that this trait is transmitted to the scion when grafted. Shoot branching plasticity in response to nitrogen supply was also studied. As strigolactones are known to have a role in the regulation of shoot development in response to nutrient availability, their involvement in the control of scion architecture by the rootstock was investigated. Functional characterization of putative grapevine strigolactone biosynthetic genes in Arabidopsis mutants or grapevine cell suspensions showed similar functions to those of Arabidopsis. Both rootstocks produced strigolactone-like compounds; the quantity produced in response to nitrogen treatments differed between the two rootstock genotypes and correlated with the expression of putative strigolactone biosynthetic genes. Exudation of strigolactone-like compounds by both rootstocks was closely related to the developmental pattern of the scion in grafted plants. These results suggest that differential regulation of strigolactone biosynthesis in response to nitrogen availability may contribute to the control of scion development conferred by each rootstock genotype.

Nanoemulsion preparations of cholecalciferol available in the market claim to have better bioavailability than the conventional fat-soluble cholecalciferol. However, limited data are available in humans for such preparations. We, therefore, compared the relative bioavailability of two formulations of 60,000 IU cholecalciferol (nanoemulsion oral solution, water-miscible vitamin D3 [test] vs soft gelatin capsules [reference]) in healthy adult participants. In this randomized, open-label, two sequence, single-dose, two-way crossover study (CTRI/2018/05/013839), Indian participants aged 18–45 years received single dose of nanoemulsion and capsule formulations, under fasting conditions. Blood samples collected over 120 h were assessed to determine cholecalciferol concentrations. Pharmacokinetic parameters (area under the concentration-time curve up to 120 h [AUC 0–120h ], maximum observed drug concentration [C max ], time to reach maximum drug concentration [T max ], terminal half-life [T ½el ], and terminal elimination rate constant [K el ]) were estimated using baseline corrected data and analyzed using analysis of variance. Among the 24 eligible participants, the relative bioavailability of nanoemulsion was significantly higher than the capsules by 36% (p = 0.0001) based on AUC 0–120h. Similarly, C max of the nanoemulsion was significantly higher by 43% (p = 0.0001) than that of the capsules. The intra-participant variability for AUC 0–120h and C max were 23.22% and 26.51%, respectively. The T max , T ½el , and K el were comparable for both the formulations. No adverse effects were noted with either of the two formulations. Nanoemulsion oral solution of cholecalciferol showed a greater bioavailability compared with soft gelatin capsules, under fasting conditions, in healthy human participants. [ABSTRACT FROM AUTHOR]

Phenolic compounds are popular in screening novel hypoglycemic agents, but the impact of oxidative degradation on the determination of α-glucosidase inhibitory activity and bioavailability is unclear. Here we showed 12 phenolic compounds structure-dependently degraded during standard simulated digestion, while in physiological hypoxia their retention rates were all over 87.89 %. This enhancement of digestive stability resulted in the biggest drop of 31.72 % in IC 50 against α-glucosidase and a significant increase in bioavailability. Enzyme kinetic and multi-spectroscopic analysis confirmed oxygen weakened the affinity of compounds to α-glucosidase, but the mechanisms were not changed. Moreover, a two-chamber culture system was designed to meet conflicting demands for oxygen between epithelium and cavity, and better α-glucosidase inhibitory activities (51.61 % maximum reduction in glucose production) and absorption rates (up to 1.10 % from undetectable) were obtained than those of uncontrolled oxygen. Hence, the oxygen level should be monitored to assess the activities of phenolic compounds in vitro., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Composition and structure of oleogels significantly influence their digestive behaviour, impacting triacylglycerol breakdown and the bioavailability of incorporated compounds. Texture profile analysis showed that sterol-based oleogels (STOs) exhibited 20 times higher hardness than beeswax-based oleogels (BWOs), which showed stronger cohesion due to elasticity sustained by adhesive forces. Tribological assessments revealed similar initial coefficients of friction (COF) for both oleogels. However, fluctuations were observed in BWOs and a gradual decrease in STOs over time, enhancing lubrication, while BWOs recorded higher adhesion. These findings provide insights into their distinct digestive behaviour, with both oleogels undergoing structural disintegration and STOs displaying a higher lipolysis degree. Non-cytotoxicity was confirmed under Caco-2 cells. β-carotene bioaccessibility was influenced by the oleogels' structural modification and values of 4.0 ± 0.7 % for STOs and 2.6 ± 1.1 % for BWOs were recorded. Results highlight the need to optimize formulations to improve bioactive's bioavailability, emphasizing the role of structured gels in modulating digestion dynamics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The interaction between dietary bioactive compounds and mycotoxins in food safety is crucial due to the potential health risks raised by mycotoxins and the protective functions of bioactive substances. This study is focused on red beetroot (Beta vulgaris), a rich source of polyphenols and betalains, incorporated into a daily consumption food such as bread, to examine its effects on the bioavailability of mycotoxins using an in vitro Caco-2 cell model. This study investigates how these compounds affect the bioavailability of mycotoxins, specifically ochratoxin A (OTA), aflatoxin B1 (AFB1), and zearalenone (ZEA), which are known to compromise intestinal barrier function and nutrient absorption. Additionally, bioaccesibility and bioavailability of total betalains (betacyanins and betaxanthins) (TBC) and polyphenols (TPC) content was evaluated. The beetroot-enriched breads were subjected to an in vitro digestion process, followed by a transepithelial transport assay to assess the bioavailability in differentiated Caco-2 cells. Results indicate an increase in the bioaccesibility of TBC and TPC (up to 99 % and 27 %, respectively) during digestion, suggesting enhanced absorption and protective effects against mycotoxin-induced damage. The presence of beetroot bread polyphenols and betalains increased the bioavailability of mycotoxins, with complex interactions observed, particularly in triple mycotoxin's combination. The results highlight the complex interactions between dietary components and mycotoxins' bioavailability, underlining the importance of further research into their mechanisms of action and potential applications in food safety and nutrition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A novel micrometer-sized porous cyclodextrin polymer (PCDP) was synthesized through the cross-linking of carboxymethyl β-cyclodextrin with 1,6-diaminohexane. We hypothesized that PCDP could be utilized as a drug carrier to enhance the dissolution rate and oral bioavailability of poorly soluble drugs. Ibuprofen (IBU), selected as the model poorly soluble drug, was successfully loaded into PCDP, resulting in a significant improvement in IBU release within simulated gastric fluid. Compared to IBU alone, IBU-loaded PCDP markedly increased the oral bioavailability of IBU, with an approximately 4-fold increase in the area under the curve (AUC) and a 3-fold increase in C max , thereby enhancing the anti-inflammatory effects in rat models. Additionally, PCDP demonstrated good biocompatibility with Caco-2 cells. These findings suggest that the micrometer sized PCDP may be a promising drug carrier for improving the dissolution and oral bioavailability of poorly soluble drugs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xiangjun Zhang reports financial support was provided by Chongqing Medical University. Xiangjun Zhang, Sisi Yi and Tao Guo has patent pending to National Intellectual Property Administration, PRC. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Selenium (Se) is an essential micronutrient for humans, and one of the new strategies to increase its intake is to fortify foodstuff with Se-bioaccessible species. This study aimed to produce Se-microparticles (selenate, selenite and Se-organic) using combined methods of microencapsulation; fortify commercial plant-based beverages (PBBs); evaluate the stability of microparticles; and estimate the bioaccessibility of Se and its contribution to the Recommended Daily Intake (RDA). Samples and bioaccessible fractions were submitted to acid digestion and Se levels (total and bioaccessible) were quantified by ICP-MS. The bioaccessibility of the Se-microparticles produced was estimated using an in vitro method under standardized conditions (INFOGEST). During the storage period, the microparticles maintained their stability and similar size. The PBBs fortified with Se-microparticles presented high bioaccessibility (77-94 %); being superior, in comparison, to the traditional fortification (Se-isolated salts). Thus, the results suggest promising perspectives for Se-supplementation in PBBs to meet nutritional needs effectively., Competing Interests: Declaration of competing interest The authors declare that they have no know competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Amyotrophic lateral sclerosis (ALS) presents a substantial challenge due to its complex nature, limited effective treatment options, and modest benefits from current therapies in slowing disease progression. This study explores the potential of intranasal (IN) delivery to enhance the CNS delivery of riluzole (RLZ), a standard ALS treatment which is subject to blood-brain barrier efflux mechanisms. Additionally, the impact of elacridar (ELC), an efflux pump inhibitor, on IN RLZ CNS bioavailability was examined. To quantify RLZ in vivo in mice, [ 14 C]-RLZ was synthesised using an optimised one-pot method. [ 14 C]-RLZ yield was 21.3 ± 3.4 %, measured by High Performance Liquid Chromatography (HPLC), with a specific activity of 40.4 ± 3.9 µCi/mg measured by HPLC and liquid scintillation counting. RLZ synthesis was verified using proton nuclear magnetic resonance ( 1 H NMR), and liquid chromatography-mass spectrometry. IN RLZ (5 mg/kg) produced double the maximum brain levels (1.11 ± 0.34 % Injected Dose (ID)/brain) at 30 min as oral RLZ (5 mg/kg). The uptake of RLZ in the liver was reduced by half for intranasal administration compared to oral administration. Intravenous ELC (5 mg/kg) substantially increased brain levels of IN RLZ to 3.52 ± 0.62 % ID/g brain at 60 min post-administration, compared to 1.87 ± 0.33 % ID/g brain in the absence of the efflux pump inhibitor. However, increased concentrations were also observed in the liver and blood. These results indicate that intranasal delivery of RLZ enhances brain targeting and reduces liver accumulation compared to the oral route. Brain uptake of IN RLZ was enhanced further by ELC, although not selectively as accumulation in the liver or blood was also observed. Further metabolic research using Chromatography-Mass spectrometry (LC-MS) or NMR along with excretion studies are warranted for a more comprehensive understanding of the pharmacokinetics of IN RLZ and IN RLZ/ELC. Additionally, employing suitable ALS animal models is crucial for understanding RLZ's effects on disease progression, mechanism of action, efficacy, and potential side effects to aid further development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Decreased saliva production due to salivary gland damage can result in difficulty speaking and swallowing, significantly reducing quality of life for head and neck cancer patients receiving radiotherapy. It is therefore imperative that treatment options are available to mitigate the effects of these debilitating side effects. D-limonene, a naturally occurring terpene, has shown protective effects on saliva production during radiotherapy treatment of mice, however the lipophilic nature of the molecule has necessitated a high oral dose to facilitate sufficient absorption. In this study, lipid-based drug delivery systems have been utilised to formulate D-limonene in order to reduce undesirable gastrointestinal side effects and increase solubility for enhanced absorption. Lipid-based formulations produced up to 180-fold increased solubility over pure D-limonene, coupled with enhanced storage stability and protection against oxidation. Furthermore, pharmacokinetic evaluation of optimised lipid-based formulations in Sprague Dawley rats displayed up to a 51.25-fold increase in bioavailability relative to pure oral D-limonene. Finally, elevated levels of lipid-formulated D-limonene were localised within the submandibular salivary glands, indicating potential for local action on saliva production. Overall, the administration of D-limonene utilising lipid-based formulations shows significant promise for advancing prevention and treatment strategies for xerostomia., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Clive A Prestidge reports financial support was provided by LimRad Therapeutics. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Timolol maleate (TM), a hydrophilic small molecule, is widely used in the clinical management of glaucoma. However, the complex physiological barriers of the eyes result in suboptimal bioavailability for traditional ophthalmic formulations. To address these challenges, we have developed an innovative pharmaceutical formulation. The nanoparticles (NPs) were formulated by a multi-step optimization process involving a Plackett-Burman design (PBD), steepest ascent design (SAD), and Box-Behnken design (BBD) to obtain TM-HA/CS@ED NPs. It was then encapsulated in an in situ gel (ISG) system consisting of deacetylated gellan gum (DGG) and xanthan gum (XG) to yield the TM-HA/CS@ED NPs ISG. The formulation demonstrated favorable safety in a series of ocular irritation assays and was characterized as a pseudoplastic fluid by rheological analyses, enhancing spreadability on the ocular surface and prolonging the retention time. Moreover, the NPs exposed after ISG dissolution exhibited strong mucosal adhesion and hydrophobicity, facilitating the hydrophilic TM to penetrate the corneal barrier. In vitro and in vivo retention evaluations and tear elimination pharmacokinetic study confirmed that TM-HA/CS@ED NPs ISG showed superior precorneal retention ability, and favorable sustained drug concentrations, resulting in sustained and stable transcorneal permeation into the eyes and significant intraocular pressure (IOP) lowering efficacy with a duration of 12 h. These results provide valuable insights into the design of ophthalmic drug delivery systems for water-soluble drugs and therapeutic interventions for glaucoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rapid progressing non-small cell lung adenocarcinoma (NSCLC) decreases treatment success. Cannabinoids emerge as drug candidates for NSCLC due to their anti-tumoral capabilities. We previously reported the controlled release of Arachidonylcyclopropylamide (ACPA) selectively targeting cannabinoid 1 (CB1) receptor in NSCLC cells in vitro. Hydrophobic polymers like polycaprolactone (PCL) offer prolonged circulation time and slower drug clearance which is suitable for hydrophobic molecules like ACPA. Thus, the extended circulation time with enhanced bioavailability and half-life of nanoparticular ACPA is crucial for its therapeutic performance in the tumor area. We assumed that a novel high technology-controlled release system increasing the bioavailability of ACPA compared to free ACPA could be transferred to the clinic when validated in vivo. Plasma profile of ACPA and ACPA-loaded PCL-based nanomedicine by LC-MS/MS and complete blood count (CBC) was assessed in wild-type Balb/c mice. Tumor growth in nanomedicine-applied NSCLC-induced athymic nude mice was assessed using bioluminescence imaging (BLI) and caliper measurements, histomorphometry, immunohistochemistry, TUNEL assay, and Western blot on days 7-21. Injectable NanoACPA increased its systemic exposure to tissues 5.5 times and maximum plasma concentration 6 times higher than free ACPA by substantially improving bioavailability. The potent effect of NanoACPA lasted for at least two days on ectopic NSCLC model through Akt/PI3K, Ras/MEK/Erk, and JNK pathways that diminished Ki-67 proliferative and promoted TUNEL apoptotic cell scores on days 7-21. The output reveals that NanoACPA platform could be a chemotherapeutic for NSCLC in the clinic following scale-up GLP/GMP-based phase trials, owing to therapeutic efficacy at a safe low dose window., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The use of in vitro markers able to reproduce the in vivo permeability and diffusivity of orally administered drugs, could represent an innovative starting point for the formulation of delivery systems, in particular for low soluble and low permeable drugs belonging to BCS class II and IV. Considering the great interest in the green pharmaceutical approaches and the increasing use of natural molecules as novel therapeutic drugs, in this study, rutin, hesperidin and curcumin have been selected as lipophilic model drugs to investigate their possible enhancement of their permeability and bioavailability after oral administration. As the low solubility of the three drugs hinders their application, β-cyclodextrins (CD), amphiphilic natural moieties able to form stable inclusion complexes, have been considered to promote their solubilization. Notably, hydroxypropyl-β-CD (HPBCD) and methyl-β-CD (MBCD), have been selected and the formation of the inclusion complexes with a stoichiometric ratio of 1:1 has been detected through phase-solubility studies and rationalized via docking calculations, revealing a strong complexation and an increased hydrophilicity of the systems. The diffusion experiments performed through the novel UV-Vis localized spectroscopy method confirmed a the extremely high stability of the CD-drugs complexes, especially in the cease of curcumin, which makes this as the predominant chemical specie to diffuse and permeates. The PermeaPad® plate, an in vitro cell-free assay, allowed to investigate the permeability behavior of the drugs, demonstrated that the type of β-cyclodextrins can influence the permeability through the biomimetic membrane, reflecting the effect of the unstirred water layer (UWL). Moreover, in the case of curcumin, the spectroscopic-mathematical approach suggested the formation of nano-supramolecular systems, detected by DLS, supporting the precision of the fitting model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Flavonoids, a type of natural polyphenolic molecule, have garnered significant research interest due to their ubiquitous nature and diverse biological activities, including antioxidant, anti-inflammatory, and anticancer effects, making them appealing to various scientific disciplines. In this regard, the use of a flavonoid nanoparticle delivery system is to overcome low bioavailability, bioactivity, poor aqueous solubility, systemic absorption, and intensive metabolism. Therefore, this review summarizes the classification of nanoparticles (liposomes, polymeric, and solid lipid nanoparticles) and the advantages of using nanoparticle-flavonoid formulations to boost flavonoid bioavailability. Moreover, this review illustrated the pioneering biomedical applications of nanoparticle-based flavonoid therapeutics, as well as safety and toxicity considerations of using a flavonoid nanoparticle delivery system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Although the relative bioavailability (RBA) can be applied to assess the effects of Pb on human health, there is no definition and no specific data of Pb-RBA to different soil sources and endpoints in vivo. In this study, we estimated the Pb-RBA from different soil sources and endpoints based on machine learning. The Pb-BAc and Pb-RBA in soils were found to be mostly in the range of 20-80 %, which is different from the USEPA Pb-RBA of 60 % in soils. The mean Pb-RBA for different biological endpoints in vivo predicted using the RF model were 49.94 ± 18.65 % for blood; 60.15 ± 26.62 %, kidney; 60.90 ± 21.51 %, liver; 50.70 ± 17.56 %, femur; and 62.89 ± 16.64 % as a combined measure. Pb-RBA of shooting range soils was 88.21 ± 16.92 % (mean), spiked/aged soils 77.11 ± 14.05 % and certified reference materials 73.70 ± 20.31 %; agricultural soil 68.28 ± 18.93 %, urban soil 64.36 ± 21.82 %, mining/smelting soils 53.99 ± 17.66 %, and industrial soils 47.71 ± 20.35 %. This study is first to define the Pb-RBA according to various soil sources and endpoints in vivo with the objective of providing more accurate Pb-RBA data for soil lead risk assessment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The simulation of antral conditions for estimating drug apparent equilibrium solubility after a high-calorie, high-fat meal is challenging. In this study, (1) we measured the apparent equilibrium solubility of two model lipophilic drugs, ketoconazole and danazol, in antral aspirates collected at various time points after a minced high-calorie, high-fat meal and a glass of water 30 min after initiation of meal administration, and we designated one point estimate for ketoconazole and one point estimate for danazol; (2) we evaluated the usefulness of FeSSGF-V2 and FEDGAS pH = 3 in reproducing the two point estimates; (3) we evaluated potential compositions of FeSSGF-V3 that simulate the pH, the buffer capacity toward both less acidic and more acidic values, and the antral lipid and protein contents with easily accessible, commercially available products, and (4) we identified the most useful composition of FeSSGF-V3 for reproducing the two point estimates. For both model drugs, apparent solubility in FeSSGF-V2 and in FEDGAS pH 3 deviated substantially from the corresponding point estimate. For FeSSGF-V3, hydrochloric acid, acetates, and FEDGASbuffer pH 3 were evaluated for regulating the pH and buffer capacity, FEDGASgel was used for simulating the lipid content, and Régilait skimmed milk powder was used for simulating the protein content. Level III FeSSGF-V3 prepared with hydrochloric acid, 6.1% (w/v) Régilait, and 2.83% (w/v) FEDGASgel, i.e., one-sixth of FEDGASgel concentration in FEDGAS pH 3, was comparatively the most useful medium for point estimating ketoconazole and danazol apparent solubility in antral contents after water administration in the fed state, induced as requested by regulatory authorities in oral drug bioavailability studies. Level III FeSSGF-V3 prepared by using hydrochloric acid as the principal pH controlling species could be useful in the evaluation of food effects on drug absorption with in silico physiologically based biopharmaceutics modeling approaches and, also, with biorelevant in vitro methodologies.

Background: Subcutaneous (SC) administration of antibiotics is a practical alternative to IV administration. Cefazolin is widely used for skin and soft tissue infections and other complex infections by IV administration., Methods: In this prospective, cross-over self-controlled study, a single dose of SC cefazolin was administered to 15 stable inpatients established on IV cefazolin as part of their management plan. The equivalent dose of cefazolin was diluted in 50 mL of normal saline via gravity feed over 30 min. Venous blood samples were collected at baseline and 0.5, 1, 2, 4 and 8 h following both the SC and IV doses. Antibiotic concentrations were measured using UPLC-MS/MS. Pharmacokinetic data were analysed using a non-linear mixed-effects modelling approach. Pain scores and infusion site reactions (oedema/erythema) were evaluated., Results: SC cefazolin was well tolerated. The bioavailability of SC administration was 74.8% (95% CI 66.7%-81.7%). Slower absorption from SC tissue was associated with a BMI of ≥30. Lower peak, and higher trough concentrations were observed with SC administration. Although lower bioavailability was observed with SC administration, the PTA for unbound drug concentrations greater than the MIC for more than 90% of the time between doses was higher for SC compared with IV administration at MICs between 0.25 and 4 mg/L. Simulated SC doses of 3 g twice daily had similar PTA to standard IV dosing of 2 g three times daily. A simulated 6 g continuous 24 h infusion of SC cefazolin had a favourable pharmacokinetic profile., Conclusion: SC cefazolin appears to be well tolerated, with an improved pharmacokinetic profile compared with IV administration. Either 3 g twice daily, or 6 g as a 24 h SC infusion could be considered for future evaluation., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Here, a high molecular weight polysaccharide preparation from Ophiocordyceps gracilis was utilized as a stabilizer and dispersant to create nanocomposites based on selenium nanoparticles (GSP-1a-SeNPs). The NPs showed the highest stability at a selenium/polysaccharide mass ratio of 1:1, with no significant change after 28 days of storage at 4 °C. The NPs exhibited a symmetrical spheroid structure with an average diameter of 85.4 nm. Next, the anti-inflammatory properties and mechanisms of the GSP-1a-SeNPs were examined in LPS-induced RAW264.7 cells, which efficiently internalized the NPs. In the anti-inflammatory assays, GSP-1a-SeNPs significantly reduced the production of pro-inflammatory cytokines, including TNF-α and IL-6, and lowered ROS levels by activating the Nrf2-Keap1 pathway. This pathway regulates selenoprotein expression, thereby balancing the immune microenvironment of RAW264.7 cells and mitigating inflammation. These results suggest that GSP-1a-SeNPs could serve as potential therapeutic agents or adjuvants for treating LPS-induced inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Withanone (WN), a bioactive phytochemical isolated from the medicinal herb Withania somnifera, has shown multiple pharmacological and therapeutic successes, including neuroprotective and anti-cancer activities. However, detailed pharmacokinetic (PK) properties of pure WN were not well defined. Pharmacokinetic (PK) characteristics, dose proportionality, and absolute bioavailability of pure WN were explored in rats using an efficient, reliable, and sensitive LC-MS/MS assay to address this gap. The method shows excellent linearity over 0.5-500 ng/mL (r 2  ≥ 0.99), is accurate, and requires less analysis time. A dose proportionality and absolute bioavailability of pure WN were determined in Sprague-Dawley (SD) rats through three ascending oral (10, 20, and 40 mg/kg) and single intravenous (5 mg/kg) PK studies. The peak concentration (Cmax) of WN was 60.53 ± 20.33, 116.30 ± 16.89, and 91.62 ± 6.20 ng/mL, corresponding to oral dosage of 10, 20, and 40 mg/kg, respectively. WN shows poor systemic exposure upon oral administration, leading to low oral bioavailability (<15 %). Additionally, the dose proportionality studies of WN revealed its saturable bioavailability and non-proportional systemic exposure over the dosage range of 10-40 mg/kg in rats. The obtained PK findings of this study would be valuable for better understanding the pharmacological effects of WN, dose regimen optimization for future studies, and relevance for clinical reference to support its future development as a potential therapeutic molecule., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Muhammad Wahajuddin reports financial support was provided by The Council of Scientific and Industrial Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

In historic mining towns, where mining activities were abandoned many decades or even centuries ago, legacy contaminations can be remobilized and redispersed, representing a threat for the environment and human health. This study focuses on urban soils (n = 19) in the town of Jihlava, the Czech Republic, one of the medieval centers of silver mining in central Europe. The basic geochemical characterization of the soils was combined with mineralogical investigations to understand the solid speciation of the metal(loid) contaminants, oral bioaccessibility tests, and exposure assessment. The total concentrations of the metal(loid)s in the original soils were not excessively high (up to 45.8 mg As/kg, 19.2 mg Cd/kg; 205 mg Cr/kg; 91.8 mg Cu/kg, 163 mg Pb/kg, 253 mg V/kg, 262 mg Zn/kg), although, in some cases, they exceeded the regulatory guidelines for agricultural and/or residential soils. A substantial increase in the metal(loid)s contents was confirmed for the < 48-µm soil fraction that was later used for the bioaccessibility tests. Scanning electron microscopy and the electron microprobe showed that ore-derived primary sulfides were rare in the studied soils. Still, hydrous ferric oxides rich in Cu, Pb and Zn and fragments of metallurgical slags composed of metal-containing glass and silicates (olivine) were prone to dissolution during extraction in a simulated gastric fluid (SGF, glycine solution acidified to pH 1.5 by HCl). The maximum bioaccessible concentrations corresponded to 4.69 mg As/kg, 1.75 mg Cd/kg, 2.02 mg Cr/kg, 20.3 mg Cu/kg, 81.6 mg Pb/kg, 16.2 mg V/kg, and 233 mg Zn/kg. Exposure estimates were carried out for children (10 kg) as a target group and a conservative soil ingestion rate (100 mg/d). However, the daily intake of all the studied contaminants was far below the tolerable limits. Our results show that the human health risk based on incidental soil ingestion in the studied area seems limited., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s).)

This study aimed to investigate the effect of dietary L-Leu supplementation on amino acid composition, serum metabolism, and meat quality characteristics in beef cattle. Twenty-four Angus cows of similar initial weight (575.5 ± 22.1 kg) were randomly assigned to two treatment groups with six replicate pens (two cattle per pen). The groups were fed a basal diet (CON) or a basal diet supplemented with 6.0 g/100 kg BW per day of L-Leu for 120 days pre-slaughter. Feeding L-Leu significantly increased average daily gain and decreased feed-to-weight-gain ratio (P < 0.05). L-Leu improved plasma free leucine bioavailability (P < 0.05), increased the concentrations of tyrosine and glutamine (P < 0.05), and decreased the concentrations of threonine and valine (P < 0.05). It also increased the content of total protein in plasma (P < 0.05). Supplementation with L-Leu tended to increase the marbling score (P = 0.06) and decrease subcutaneous fat thickness (P = 0.06), as well as the content of C10:0 (P < 0.05), C14:0 (P = 0.05), C20:0 (P < 0.05), and C18:2n-6 t (P = 0.07) in the longissimus thoracis muscle. However, L-Leu significantly increased the crude protein content in the longissimus thoracis muscle (P < 0.05). Correlation analysis revealed that L-Leu downregulated the relative abundance of metabolites associated with subcutaneous fat thickness and beef fatty acid synthesis (P < 0.01), and upregulated the relative abundance of metabolites associated with crude protein and ether extract in the longissimus thoracis muscle (P < 0.01). In conclusion, dietary L-Leu supplementation increases leucine bioavailability and improves meat quality in fattening beef cattle by altering host serum metabolism., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Obexelimab is an investigational, bifunctional, non-depleting, humanized monoclonal antibody that binds CD19 and FcγRIIb to inhibit B cells, plasmablasts, and CD19-expressing plasma cells. In clinical trials, intravenous (IV) administration of obexelimab has been well-tolerated, and demonstrated clinical activity in patients with rheumatoid arthritis, systemic lupus erythematosus, and immunoglobulin G4-related disease. This study was performed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of obexelimab following subcutaneous (SC) administration, and compare PK/PD profiles between healthy Japanese and non-Japanese volunteers., Methods: This was a Phase I, open-label, parallel group, multiple-dose study. Participants were randomized to five cohorts to receive three doses of obexelimab as 125 mg SC every 14 days (q14d), 250 mg SC q14d, 375 mg SC q14d, 250 mg IV q14d, and 125 mg SC every 7 days, then monitored during a 28-day safety follow-up period. PK/PD assessments were performed after the first and third doses., Results: A total of 50 healthy volunteers (25 Japanese and 25 non-Japanese) were enrolled and distributed evenly between dose cohorts. All SC dosing regimens were well-tolerated. Dose-proportional PK was observed following SC doses with a bioavailability of approximately 60%. No clinically meaningful differences in PK parameters were found between healthy Japanese and non-Japanese participants. Antidrug antibodies (ADA) were detected in 6/50 (12%) participants after dosing. ADA had no or minimal impact on PK in all six ADA positive participants. Near-complete CD19 receptor occupancy and an absolute B-cell count nadir of approximately 50% baseline levels were maintained for the duration of the study in both populations., Conclusion: Obexelimab SC administration demonstrated favorable bioavailability, was well-tolerated, and showed no clinically meaningful ethnic differences in PK/PD. These results support further clinical development of SC obexelimab to treat B-cell mediated autoimmune diseases., Trial Registration: NCT02867098., Competing Interests: Declarations. Conflict of Interest: Xiaodong Wang, Rachel Kirk, Mark Matijevic, Minggeng Gao, Allen Poma, Shauna Quinn, Sujata Arora, Tanya Fischer are employees of Zenas BioPharma, Waltham, MA. Ethical Approval: The study was conducted according to the ethical principles from the Declaration of Helsinki and in compliance with all International Council for Harmonisation Good Clinical Practice Guidelines and local regulatory requirements. All participants provided written informed consent., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

The poor techno-functional properties of walnut protein isolate (WPI) limit its application as carrier to improve bioavailability of curcumin. In this study, WPI was modified by pH-shifting (PS) and protein-glutaminase (PG). Changes on the physicochemical and structural characteristics of WPI and effects on complexation with curcumin were investigated. Treatment of PS plus PG increased electrostatic repulsion of WPI with altered secondary and tertiary structure. Solubility of WPI was greatly improved from 18.09% to 52.90%. The increased flexibility resulted in reduced particle size and increased exposure of hydrophobic groups. The improved amphiphilicity of WPI provided more binding sites for complexation with curcumin. Encapsulation efficiency of curcumin was increased from 32.50% to 94.48%. Interestingly, the formed complexes were able to protect curcumin from degradation with improved storage stability and bioaccessibility. Thus, PS plus PG could serve as effective modification strategy for utilization of WPI as a promising delivery vehicle for hydrophobic bioactives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cells counter accumulation of misfolded secretory proteins in the endoplasmic reticulum (ER) through activation of the Unfolded Protein Response (UPR). Small molecules termed chemical chaperones can promote protein folding to alleviate ER stress. The bile acid tauroursodeoxycholic acid (TUDCA) has been described as a chemical chaperone. While promising in models of protein folding diseases, TUDCA's mechanism of action remains unclear. Here, we found TUDCA can rescue growth of yeast treated with the ER stressor tunicamycin (Tm), even in the absence of a functional UPR. In contrast, TUDCA failed to rescue growth on other ER stressors. Nor could TUDCA attenuate chronic UPR associated with specific gene deletions or overexpression of a misfolded mutant secretory protein. Neither pretreatment with nor delayed addition of TUDCA conferred protection against Tm. Importantly, attenuation of Tm-induced toxicity required TUDCA's critical micelle forming concentration, suggesting a mechanism where TUDCA directly sequesters drugs. Indeed, in several assays, TUDCA-treated cells closely resembled cells treated with lower doses of Tm. In addition, we found TUDCA can inhibit dyes from labeling intracellular compartments. Thus, our study challenges the model of TUDCA as a chemical chaperone and suggests that TUDCA decreases drug bioavailability, allowing cells to adapt to ER stress., Competing Interests: Conflicts of interest: The authors declare no financial conflicts of interest.

Background: Cationic calcium ions can crosslink anionic alginate and pectin molecules. It was hypothesized that calcium crosslinking would improve the stability and functionality of biopolymer nanoparticles consisting of zein cores coated by alginate-pectin shells. The effects of calcium ion addition on the structural, physicochemical, and gastrointestinal properties of quercetin-loaded zein/alginate-pectin nanoparticles were therefore investigated., Results: The nanoparticles remained stable to aggregation at calcium ion concentrations of 9 mmol/L or less but aggregated and sedimented at higher concentrations. Calcium ion reinforcement increased the particle dispersion stability even at NaCl concentrations up to 1.4 molL -1 . The presence of the calcium ions also reduced quercetin release during the early stages of simulated gastrointestinal digestion but increased its release during the later stages. The relatively high release (56.1%) of quercetin from the calcium-reinforced nanoparticles after digestion resulted in higher intracellular antioxidant activities. The pharmacokinetics of the encapsulated quercetin was measured after its oral administration to rats. The maximal concentration (C max ) of quercetin in rat plasma for calcium-reinforced nanoparticles was 6.1% higher than non-reinforced nanoparticles; the half-life (t 1/2 ) increased by 17.5%, and the mean retention time (MRT) was 10.0% higher (P < 0.05)., Conclusion: These results suggest that calcium ion addition improved the performance and bioavailability of nutraceutical-loaded biopolymer nanoparticles. This might find application in the food and beverage industry. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

The diffusive gradient in thin films technique (DGT), with a resin gel based on Lewatit® FO 36 was used for the first time to predict arsenic (As) bioavailability in soils collected in different environmental contexts. The predicted bioavailability, determined by fluxes to DGT, was compared with the bioavailability and bioaccumulation in the plants (Calendula officinalis), where a strong correlation was observed (r = 0.8857 (C E /C roots ) and r = 0.9208 (C E /C shoots ); p < 0.05; n > 40). Arsenic, predominantly accumulated in the roots of plants from all soil samples, reached concentrations up to 507.8 mg kg -1 . To better understand the As distribution within the various soil-bearing phases, sequential extraction procedures were performed and revealed low mobility and availability of As, particularly in A and R soil samples, where As pollution is primarily caused by anthropogenic activities such as mining and industrial activities. The obtained results show that Calendula officinalis plants can be grown on soils contaminated by arsenic, while the low translocation factors indicate that accumulate arsenic predominantly in the root system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this study, the impact of various tea preparation techniques on the content of bioactive compounds, antioxidant capacity, antibacterial properties, and polyphenol bioavailability in green, black, and oolong tea infusions was examined. The findings demonstrated that the fermentation process significantly influences the levels of bioactive compounds, with green tea infusions exhibiting the highest, and black tea the lowest, content of phenolic compounds. A positive correlation was observed between the content of the phenolic compound and both antioxidant and antibacterial activities. Additionally, the microwave brewing method was identified as the most effective preparation technique for maximizing the bioactive compound content and bioavailability. The inclusion of skim milk powder was found to further enhance the bioavailability of phenolic compounds during digestive process. The research suggests that green tea infusions prepared using the microwave brewing method and supplemented with the skim milk powder, could serve as a functional beverage offering enhanced health benefits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Colorectal cancer (CRC) is the second most deadly and the third most diagnosed cancer in both sexes worldwide. CRC pathogenesis is associated with risk factors such as genetics, alcohol, smoking, sedentariness, obesity, unbalanced diets, and gut microbiota dysbiosis. The gut microbiota is the microbial community living in symbiosis in the intestine, in a dynamic balance vital for health. Increasing evidence underscores the influence of specific gut microbiota bacterial species on CRC incidence and pathogenesis. In this regard, conjugated linoleic acid (CLA) metabolites produced by certain gut microbiota have demonstrated an anticarcinogenic effect in CRC, influencing pathways for inflammation, proliferation, and apoptosis. CLA production occurs naturally in the rumen, and human bioavailability is through the consumption of food derived from ruminants. In recent years, biotechnological attempts to increase CLA bioavailability in humans have been unfruitful. Therefore, the conversion of essential dietary linoleic acid to CLA metabolite by specific intestinal bacteria has become a promising process. This article reviews the evidence regarding CLA and CLA-producing bacteria as therapeutic agents against CRC and investigates the best strategy for increasing the yield and bioavailability of CLA. Given the potential and limitations of the present strategies, a new microbiome-based precision nutrition approach based on endogenous CLA production by human gut bacteria is proposed. A literature search in the PubMed and PubMed Central databases identified 794 papers on human gut bacteria associated with CLA production. Of these, 51 studies exploring association consistency were selected. After excluding 19 papers, due to health concerns or discrepancies between studies, 32 papers were selected for analysis, encompassing data for 38 CLA-producing bacteria, such as Bifidobacterium and Lactobacillus species. The information was analyzed by a bioinformatics food recommendation system patented by our research group, Phymofood (EP22382095). This paper presents a new microbiome-based precision nutrition approach targeting CLA-producing gut bacterial species to maximize the anticarcinogenic effect of CLA in CRC., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

1. The objective of this study was to test the effect of microbial phytase and calcium (Ca) levels on the Zn bioavailability depending on the Zn source.2. A total of 144, one-day-old broilers received a diet containing 40 mg Zn/kg for 1 week. They were then assigned to one of the eight experimental treatments during 2 weeks. Diets contained 27 mg native Zn and were formulated according to a 2 × 2 × 2 factorial design with two added Zn sources (23 mg Zn/kg), sulphate (ZnSO 4 ) or oxide (ZnO); two dietary Ca levels of either 6 (low) or 10 g/kg (moderate); and two microbial phytase levels, of either 0 or 750 phytase unit/kg.3. Moderate Ca plus phytase improved body weight gain (BWG) and low Ca level without microbial phytase decreased tibia weight (Ca × Phy; p  = 0.049). Zinc oxide resulted in a higher tibia development ( i.e . tibia weight and length; p  < 0.05) and BWG ( p  = 0.009) and lower FCR ( p  < 0.001) compared to ZnSO 4 .4. Phytase improved tibia Zn concentration especially in birds given ZnSO 4 compared to ZnO (Zn × Phy; p  = 0.049). Moderate Ca diets improved tibial characteristics and Zn deposition compared to low Ca diets ( p  < 0.05).5. Soluble Zn in the gizzard increased in the presence of phytase ( p  = 0.011), while higher dietary Ca reduced this in birds receiving ZnO ( p  = 0.004). In the jejunum, Zn solubility was higher with phytase ( p  = 0.008).6. Under the conditions of this study, dietary levels of Ca and microbial phytase affect Zn availability in broilers more than the Zn source.

Background & Aims: Eating habits during childhood have undergone significant changes, with a notable increase in the consumption of ultra-processed foods (UPF). This situation deserves attention, given the close relationship between UPF and adverse health outcomes. This is due to the nutritional composition of UPF, which has high levels of health-critical nutrients such as sugar, fat, and sodium, thus compromising the overall quality of the diet. An excess of these nutrients can increase the risk of developing excess weight, nutritional deficiencies, and chronic diseases during childhood. Among the nutritional deficiencies is iron. This is due to the fact that UPF are not good sources of iron. This, combined with the fact that UPF is low in nutrients that help make iron more available, such as vitamin C, increases the risk of developing anemia. Therefore, this study aimed to assess the availability of iron, as well as the presence of anemia and excess weight in children living in situations of social vulnerability, and to determine their association with the consumption of UPF., Methods: This is a population-based cross-sectional study. Children aged between 6 and 59 months living in slums were included. The presence of excess weight was assessed by measuring weight and height, and the presence of anemia was determined by hemoglobin concentration, assessed using the HemoCue portable hemoglobinometer. A 24-h food recall was also used to assess the relative calorie intake of UFP and the dietary availability of iron using an algorithm. All statistical analyses were carried out using the statistical software Jamovi., Results: In this study, 443 children were included; 19.2 % were classified as with excess weight, and 55.6 % were anemic; the average absorbable iron content was 0.54 (SD ± 0.42) mg, and 39.2 % of the calories consumed came from UPF. The association analysis showed that children with calorie share relative to UPF had a decrease of -0.12 mg of bioavailable iron (β: -0.12; 95 % CI: -0.23; -0.01). It was also possible to identify that the higher calorie share of UPF increased their chances of being classified as with excess weight and anemic by up to 116 % (OR: 2.16; 95 % CI 1.05; 4.46) and 145 % (OR: 2.45; 95 % CI: 1.26; 4.78), respectively., Conclusions: The relationship found between UPF consumption and the availability of iron in the diet, excess weight, and anemia calls for attention, especially in contexts of social vulnerability. These findings demonstrate the need for greater attention to nutrition in childhood to promote an adequate and healthy diet. This can help to change the nutritional and epidemiological panorama of the population, contributing to a better general state of health for future generations of adults., Competing Interests: Declaration of competing interest None., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

The gastrointestinal tract (GIT) plays a pivotal role in the absorption of orally administered drugs, with the small intestine serving as the primary site due to its extensive surface area and specialized cell types, including enterocytes and M cells. After oral administration, drugs are generally transported via the portal vein to the liver, where they undergo first-pass metabolism. This process involves various enzymatic reactions, including glucuronidation, facilitated by uridine diphosphate-glucuronosyltransferase (UGT), a major phase 2 reaction in mammalian metabolism. UGTs conjugate glucuronic acid to a wide array of endogenous and exogenous substrates, enhancing their solubility and excretion, but significantly affecting the bioavailability and therapeutic efficacy of drugs. UGT enzymes are ubiquitously distributed across tissues, prominently in the liver, but also in the GIT, kidneys, brain, and other organs where they play crucial roles in xenobiotic metabolism. Species-specific differences in UGT expression and activity impact the selection of animal models for pharmacological studies. Various experimental models - ranging from computational simulations (in silico) to laboratory experiments (in vitro) and animal studies (in vivo) - are employed throughout drug discovery and development to evaluate drug metabolism, including UGT activity. Effective strategies to counter pre-systemic metabolism are critical for improving drug bioavailability. This review explores several approaches including prodrugs, co-administration of specific molecules or use of inhibiting excipients in formulations. Strategies incorporating these excipients in nanoformulations demonstrate notable increases in drug absorption and bioavailability. This review highlights the importance of targeted delivery systems and excipient selection in overcoming metabolic barriers, aiming to optimize drug efficacy and patient outcomes., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cyclolinopeptides (CLs) have anti-inflammatory, anti-osteoporosis, and anti-tumor effects, however, low water and oil solubility greatly limit their application. Herein, CLs-loaded β-cyclodextrin (β-CD) emulsions were prepared with different oil phases. The in vitro digestibility, cellular absorption, and anti-inflammatory effects were evaluated. Camellia oil diacylglycerol (CO DAG) showed enhanced dissolving ability for CLs due to high polarity. β-CD formed inclusion complexes with DAG through hydrogen bond and the emulsions showed smaller size and higher physical stability with 50 % (w/w) oil. The in vitro digestibility of the DAG emulsion was increased and the CLs' bioavailability was 13.6-fold higher than CLs in oil. The CLs-loaded Pickering emulsion digesta exhibited a higher nitric oxides (NO) inhibition rate (58.62 %) and Caco-2 cell penetration (3.09 × 10 -6  cm/s). Therefore, emulsion formulated with β-cyclodextrin and DAG can effectively improve the solubility and bioavailability of CLs, which has significant potential for application in functional foods and pharmaceutical industry., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

(20 S)-Ginsenoside Rh2 is a natural saponin derived from Panax ginseng Meyer (P. ginseng), which showed significantly potent anticancer properties. However, its low water solubility and bioavailability strongly restrict its pharmaceutical applications. The aim of current research is to develop a modified (20 S)-Ginsenoside Rh2 formulation with high solubility, dissolution rate and bioavailability by combined computational and experimental methodology. The "PharmSD" model was employed to predict the optimal polymer for (20 S)-Ginsenoside Rh2 solid dispersion formulations. The solubility of (20 S)-Ginsenoside Rh2 in various polymers was assessed, and the optimal ternary solid dispersion was evaluated across different dissolution mediums. Characterization techniques included the Powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR). Molecular dynamics simulations were employed to elucidate the formation mechanism of the solid dispersion and the interactions among active pharmaceutical ingredient (API) and excipient molecules. Cell and animal experiments were conducted to evaluate the in vivo performance of the modified formulation. The "PharmSD" solid dispersion model identified Gelucire 44/14 as the most effective polymer for enhancing the dissolution rate of Rh2. Subsequent experiment also confirmed that Gelucire 44/14 outperformed the other selected polymers. Moreover, the addition of the third component, sodium dodecyl sulfate (SDS), in the ternary solid dispersion formulation significantly amplified dissolution rates than the binary systems. Characterization experiments revealed that the API existed in an amorphous state and interacted via hydrogen bonding with SDS and Gelucire. Moreover, molecular modeling results provided additional evidence of hydrogen bonding interactions between the API and excipient molecules within the optimal ternary solid dispersion. Cell experiments demonstrated efflux ratio (EfR) of Rh2 ternary solid dispersion was lower than that of pure Rh2. In vivo experiments revealed that the modified formulation substantially improved the absorption of Rh2 in rats. Our research successfully developed an optimal ternary solid dispersion for Rh2 with high solubility, dissolution rate and bioavailability by integrated computational and experimental tools. The combination of Artificial Intelligence (AI) technology and molecular dynamics simulation is a wise way to support the future formulation development., Competing Interests: Declarations. Ethics approval and consent to participate: No ethical approval is required for this study. Consent to publish: All the authors read and approved the final version of the manuscript. Competing interests: The authors report no conflicts of interest., (© 2024. Controlled Release Society.)

Clofazimine is an emerging drug for the treatment of cryptosporidiosis in infants. As a poorly water-soluble drug, the formulation of clofazimine in age-appropriate vehicles is challenging and often results in the use of off-label formulations. Milk-based vehicles such as human milk and bovine milk have been investigated as age-appropriate formulations and shown to increase the solubilisation of poorly water-soluble drugs via enhanced solubility in lipid digestion products in vitro. We hypothesised that administration of clofazimine within a milk-based vehicle would enhance bioavailability for infant patients. Towards this objective, suspensions of clofazimine in human and bovine milk were orally administered separately to piglets and rats and the subsequent plasma concentrations were compared to those after administration of an aqueous drug suspension. Initial investigations with a rodent model showed a significant increase (258%) in the oral bioavailability of clofazimine when administered with human milk. Similarly, the oral bioavailability of clofazimine was significantly higher when administered in both human (154%) and bovine milk (175%) using a neonatal piglet model, suggesting comparable enhancement in oral bioavailability could be achieved with human or bovine milk. These findings demonstrate the potential of human milk in particular to provide an effective administration vehicle for clofazimine administration to infants without the need for additional excipients., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

With the continuous advancements in detection methods and the exploration of unknown substances, an increasing number of bioactive compounds are being discovered. Fatty acid esters of hydroxyl fatty acids (FAHFAs), a class of endogenous lipids found in 2014, exhibit various physiological activities, such as improving glucose tolerance and insulin sensitivity, stimulating insulin secretion, and demonstrating broad anti-inflammatory effects. Moreover, some FAHFAs are closely linked to intestinal health and can serve as potential biomarkers for gut health. Various FAHFAs have been observed in food, including palmitic acid esters of hydroxy stearic acids (PAHSA), oleic acid esters of hydroxy stearic acids (OAHSA), linoleic acid esters of hydroxy linoleic acid (LAHLA). As a type of lipid regularly consumed in the daily diet, it is highly important to ascertain the types and quantities of FAHFAs present in the diet. This article, based on existing research, provides a review of the analysis methods for FAHFAs, particularly focusing on the separation of chiral isomers. It also summarizes the sources and contents of dietary FAHFAs, emphasizing their bioavailability and impact on the gut. Understanding the beneficial effects of these lipids in the diet can serve as a valuable reference for the development of specific functional foods., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We demonstrate the proof of concept of increasing the bioavailability of carbon substrates, derived from plastic waste, for their conversion to the biodegradable polymer polyhydroxyalkanoate [PHA] by bacteria and test various approaches to PHA accumulation through batch, fed batch and continuous culture. Styrene, ethylbenzene, and toluene are produced from the pyrolysis of mixed plastic waste (Kaminsky, 2021; Miandad et al., 2017), but they are volatile and poorly soluble in water making them difficult to work with in aqueous fermentation systems. By chemically converting these aromatic compounds to benzoic acid, and subsequently to its sodium salt, we increased the solubility and reduced the volatility of the substrate supplied to Pseudomonas putida CA-3 to accumulate polyhydroxyalkanoates. 1 L scale batch, fed batch, and continuous fermentations were carried out; the fed batch fermentation resulted in the maximum volumetric PHA productivity of 61.67 ± 7.34 mg L -1 h -1 ; while batch and continuous, at a dilution rate, d = 0.2 h -1 , fermentations resulted in 13.30 ± 0.01 and 4.06 ± 0.01 mg L -1 h -1 of PHA respectively., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kevin E O’Connor reports a relationship with Bioplastech Ltd that includes: equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Despite the potential benefits of nasal drug delivery, there is a need for a systematic evaluation of the efficacy of powder formulations adhering to the nasal mucosa. This study aims to establish a systematic evaluation method for nasal drug absorption from powder formulations. We selected three model compounds-antipyrine, griseofulvin, and acyclovir-and analyzed their pharmacokinetics following nasal administration of powder formulations under physiological conditions. Our experimental design incorporated assessments of the drug absorption patterns. Antipyrine demonstrated rapid absorption exclusively from the nasal cavity. In contrast, griseofulvin exhibited absorption from the nasal cavity and the gastrointestinal tract. This phenomenon could be attributed to the rapid nasal clearance of the drug with an initial half-life of 5 min. To further establish the physiological validity of our method, we conducted an experiment to investigate the impact of changing the mucociliary clearance (MC) on nasal absorption that resulted in a 1.2-fold increase in the bioavailability of acyclovir upon prolonged MC. Our findings support the utility of established methods in evaluating nasal absorption and their behavior in the nasal cavity. This study holds a promising advancement toward effective drug delivery via nasal administration, potentially leading to targeted delivery and improved therapeutic outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Budesonide oral suspension (BOS) is a swallowed corticosteroid indicated for 12-week therapy in eosinophilic esophagitis with minimal systemic exposure following administration. We aimed to assess the relative bioavailability of a single dose of BOS administered under fasting and fed (high-fat/high-calorie meal) conditions. Healthy adult volunteers (N = 20) were enrolled in an open-label, single-center, crossover study and were randomized (1:1) to receive a single oral dose of BOS 2.0 mg under fasting or fed conditions, with a 48-h washout period before crossover to the alternative conditions. Serial plasma samples were collected before and up to 24 h after dosing. Pharmacokinetic (PK) parameters were calculated from plasma budesonide concentration-time profiles by noncompartmental analysis. The mean peak budesonide concentration (C max ) was ∼13% lower under fed than under fasting conditions (604.1 vs 692.9 pg/mL). Areas under the concentration-time curves from dosing to the last measurable budesonide concentration and from dosing to infinity were ∼26% higher and ∼27% higher under fed than fasting conditions (3529 vs 2811 pg h/mL and 3892 vs 3075 pg h/mL, respectively). The median time to peak plasma budesonide concentration was significantly longer (∼1 h) under fed than fasting conditions (2.516 vs 1.286 h, P < .001). Safety and tolerability were also assessed throughout the study; all adverse events were mild or moderate in severity. Despite slight differences in budesonide PK parameters between fed and fasting conditions, the effect of food on systemic exposure to budesonide (BOS formulation) is not expected to be clinically meaningful., (© 2024 Takeda Pharmaceuticals USA, Inc. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Various bodily functions are maintained, and health benefits are provided by food-derived bioactive components. Fruits and vegetables contain numerous beneficial components, including vitamins, minerals, antioxidants, enzymes, and phytonutrients. However, the body's ability to absorb these substances at a given rate and degree frequently limits their bioavailability. If food-derived bio actives are used as therapeutic or dietary interventions, this limitation can result in low efficacy and suboptimal results. Recently, nanotechnology has been a useful method for increasing the bioavailability of bioactive compounds produced from food. Active ingredients can be delivered and absorbed more efficiently with the help of nanotechnology. By altering their size or surface properties, bioactive components can be made more soluble, permeable, and bioavailable through nanotechnology. The present review will provide an overview of the various bioactive components, the application of nanotechnology to improve the availability of bioactive molecules to humans and animals, and the challenges and safety concerns associated with nanotechnology in the production of food-derived bioactive molecules., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Albendazole, an anthelmintic recognized by the World Health Organization as an essential medicine, is known to have limitations in solubility and bioavailability. To improve these properties, binary and ternary multicomponent systems were designed employing different combinations of albendazole desmotropes with maltodextrin and aspartic acid. The impact of these systems in solution was evaluated through phase solubility analysis. Moreover, solid systems were produced using the kneading method and evaluated with a combination of techniques, including dissolution tests, Fourier-Transform infrared spectroscopy, X-ray powder diffraction, and scanning electron microscopy. These studies demonstrated that multicomponent systems had higher solubility than free desmotropes, with the system formulated using solid form II of albendazole exhibiting the most significant improvement. Additionally, the dissolution percentage of each solid system in simulated gastric fluid was significantly increased. It can therefore be concluded that these innovative systems offer promising alternatives for improving the oral bioavailability of albendazole, generating significant interest in the pharmaceutical field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Curcumin (Cur) has many potential applications in the food industry. However, it suffers from poor water solubility, low plasma and tissue uptake and susceptibility to oxidation. In this study, β-lactoglobulin (β-LG)-hyaluronic acid (HA) binary covalent complexes were prepared by ultrasound-assisted Maillard reaction and used as the carrier to deliver Cur. Results of SDS-PAGE, degree of grafting, and SEM showed that β-LG was successfully grafted to HA, and the degree of grafting increased from 15.30 ± 0.28 % to 29.70 ± 0.45 % under ultrasound treatment. There was a decrease in α-helix and β-sheet contents, and an increase in random coil content, and the amide I bands, and tryptophan motifs in the covalent secondary and tertiary structures of the nanocomplexes. Encapsulation by β-LG-HA could form the controlled release of Cur, resulting in a decreased release rate in the oral and gastric phases and an increased release rate in the intestinal phase, as demonstrated in an in vitro digestion simulation. Furthermore, the β-LG-HA-Cur nanocomplex exhibited the superior antioxidant and enzyme inhibition of α-amylase and α-glucosidase. The inhibition rates of α-amylase and α-glucosidase could reach 48.91 ± 0.81 % and 49.88 ± 0.61 %, respectively. This study will help to understand the ultrasound-assisted Maillard reaction covalent binding of protein- polysaccharides complexes, demonstrate the potential for Cur delivery, and develop functional dairy products with hypoglycemic activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

To design a novel emulsifier capable of enhancing the bioavailability of curcumin (Cur)-loaded emulsions in the gastrointestinal tract, soy protein-based ternary composite nanoparticles (SEP n ) were fabricated by transacylation reaction. The results showed that SEP n was formed by the covalent binding of the carboxyl groups in PGA to the amino groups in SEC through multiple forces. SEP n-1:1 was determined to be the optimal condition for preparing Cur-loaded emulsions. Additionally, SEP n-1:1 had superior emulsifying capacity as formed plastic-state emulsion gel with φ as low as 0.5. Moreover, the rise in oil content promoted the development of gel, thus increasing the apparent viscosity, gel strength, and stability of Cur-loaded emulsions. Furthermore, SEP n-1:1 emulsion exhibited excellent gastric stability and higher free fatty acid (FAA) release rates in the small intestine phase compared with that of SEC con (SEC control sample) and Mixture emulsion, thus leading to the highest bioavailability of Cur (28.57 ± 1.91 %)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: S-pindolol has metabolic effects of potential benefit in cancer cachexia: reduced catabolism through nonselective β-blockade; increased anabolism through partial β2 receptor agonism; and increased appetite and reduced fatigue through central 5-hydroxytryptamine/serotonin receptor activity. A Phase 2a clinical trial demonstrated that S-pindolol can reverse weight loss and improve fat-free mass in patients with cancer-related weight loss. A comparative phase I bioavailability study of S-pindolol and racemic pindolol was performed to support the development of S-pindolol in cancer cachexia., Methods: This two-part study assessed the comparative bioavailability and pharmacokinetics of single doses of S-pindolol benzoate (ACM-001.1) or pindolol (Part 1) and the steady-state pharmacokinetics and pharmacodynamics of multiple doses of ACM-001.1 and pindolol (Part 2) in healthy volunteers (NCT06028321). ACM-001.1 5, 10 and 15 mg and pindolol 15, 20 and 30 mg were tested. In Part 1, subjects were randomised to ACM-001.1 15 mg followed after a 48-h washout period by pindolol 30 mg, or the reverse sequence; another group received pindolol 15 mg. Subjects in Part 2 were randomised to pindolol 20 mg twice-daily or ACM-001.1 5, 10 or 15 mg twice-daily for 4 days. Bioavailability, pharmacokinetics, pharmacodynamics, potential for and extent of stereoconversion, and tolerability were assessed., Results: Parts 1 and 2 included 24 and 27 healthy volunteers, respectively. ACM-001.1 had predictable pharmacokinetics up to a dose of 15 mg twice daily, with low intersubject variability, after single and multiple doses (T max 1 vs. 1.5 h; C max 74 vs. 73.6 ng/mL; AUC (0-t) 440 vs. 414 ng·h/mL; t 1/2 4.042 vs. 3.566 h). The bioavailability of S-pindolol after equivalent doses of pindolol (20 mg) and ACM-001.1 (10 mg) was comparable, and formal bioequivalence margins were met (90% CI for C max , AUC (0-t) and AUC (0-inf) within 80%-125% bioequivalence acceptance criteria). No evidence of stereoconversion of the S-enantiomer into the R-enantiomer, no accumulation, dose linearity and dose proportionality of S-pindolol over a range of doses were demonstrated; we also show indirectly that there was no food effect. ACM-001.1 was generally well tolerated, with no apparent relationship of side effects to dose, no serious adverse events, severe treatment-emergent adverse events (TEAEs) or deaths, and similar incidences of TEAEs (fatigue, dizziness, somnolence, nausea and headache) with ACM-001.1 10 and 15 mg and pindolol 20 mg., Conclusions: Data from this bridging study of enantiomerically pure ACM-001.1 and its parent racemic drug, pindolol, support clinical trials of ACM-001.1 for the treatment of cancer cachexia., (© 2024 Quotient Sciences and Actimed Therapeutics. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Lupeol, a naturally occurring triterpenoid, has garnered significant attention for its diverse range of biological activities and potential therapeutic applications. This comprehensive review delves into the various aspects of lupeol, including its sources, extraction methods, chemical characteristics, pharmacokinetics, safety evaluation, mechanisms of action, and applications in disease treatment. We highlight the compound's unique carbon skeleton and its role in inflammation regulation, antioxidant activity, and broad-spectrum antimicrobial effects. The review also underscores lupeol's potential in cancer therapy, cardiovascular protection, metabolic disease management, and wound healing. Furthermore, we discuss the challenges and future perspectives of lupeol's clinical application, emphasizing the need for further research to improve its bioavailability and explore its full therapeutic potential. The review concludes by recognizing the significance of lupeol in drug development and healthcare, with expectations for future breakthroughs in medical applications., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)