Evaluation of water properties in HEA–HEMA hydrogels swollen in aqueous-PEG solutions using thermoanalytical techniques

Hydrogels are polymeric materials used in many pharmaceutical and biomedical applications due to their ability to form 3D hydrophilic polymeric networks, which can absorb large amounts of water. In the present work, polyethylene glycols (PEG) were introduced into the hydrogel liquid phase in order to improve the mechanical properties of hydrogels composed of 2-hydroxyethylacrylate and 2-hydroxyethylmethacrylate (HEA–HEMA) synthesized with different co-monomer compositions and equilibrated in water or in 20 % water–PEG 400 and 600 solutions. The thermoanalytical techniques [differential scanning calorimetry (DSC) and thermogravimetry (TG)] were used to evaluate the amount and properties of free and bound water in HEA–HEMA hydrogels. The internal structure and the mechanical properties of hydrogels were studied using scanning electron microscopy and friability assay. TG “loss-on-drying” experiments were applied to study the water-retention properties of hydrogels, whereas the combination of TG and DSC allowed estimating the total amount of freezable and non-freezing water in hydrogels. The results show that the addition of viscous co-solvent (PEG) to the liquid medium results in significant improvement of the mechanical properties of HEA–HEMA hydrogels and also slightly retards the water loss from the hydrogels. A redistribution of free and bound water in the hydrogels equilibrated in mixed solutions containing 20 vol% of PEGs takes place

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Water-soluble drug partitioning and adsorption in HEMA/MAA hydrogels.

Two-photon confocal microscopy and back extraction with UV/Vis-absorption spectrophotometry quantify equilibrium partition coefficients, k, for six prototypical drugs in five soft-contact-lens-material hydrogels over a range of water contents from 40 to 92%. Partition coefficients were obtained for acetazolamide, caffeine, hydrocortisone, Oregon Green 488, sodium fluorescein, and theophylline in 2-hydroxyethyl methacrylate/methacrylic acid (HEMA/MAA, pKa≈5.2) copolymer hydrogels as functions of composition, aqueous pH (2 and 7.4), and salinity. At pH 2, the hydrogels are nonionic, whereas at pH 7.4, hydrogels are anionic due to MAA ionization. Solute adsorption on and nonspecific electrostatic interaction with the polymer matrix are pronounced. To express deviation from ideal partitioning, we define an enhancement or exclusion factor, E ≡ k/φ1, where φ1 is hydrogel water volume fraction. All solutes exhibit E > 1 in 100 wt % HEMA hydrogels owing to strong specific adsorption to HEMA strands. For all solutes, E significantly decreases upon incorporation of anionic MAA into the hydrogel due to lack of adsorption onto charged MAA moieties. For dianionic sodium fluorescein and Oregon Green 488, and partially ionized monoanionic acetazolamide at pH 7.4, however, the decrease in E is more severe than that for similar-sized nonionic solutes. Conversely, at pH 2, E generally increases with addition of the nonionic MAA copolymer due to strong preferential adsorption to the uncharged carboxylic-acid group of MAA. For all cases, we quantitatively predict enhancement factors for the six drugs using only independently obtained parameters. In dilute solution for solute i, Ei is conveniently expressed as a product of individual enhancement factors for size exclusion (Ei(ex)), electrostatic interaction (Ei(el)), and specific adsorption (Ei(ad)):Ei≡Ei(ex)Ei(el)Ei(ad). To obtain the individual enhancement factors, we employ an extended Ogston mesh-size distribution for Ei(ex); Donnan equilibrium for Ei(el); and Henry's law characterizing specific adsorption to the polymer chains for Ei(ad). Predicted enhancement factors are in excellent agreement with experiment

Water-soluble drug partitioning and adsorption in HEMA/MAA hydrogels.

Two-photon confocal microscopy and back extraction with UV/Vis-absorption spectrophotometry quantify equilibrium partition coefficients, k, for six prototypical drugs in five soft-contact-lens-material hydrogels over a range of water contents from 40 to 92%. Partition coefficients were obtained for acetazolamide, caffeine, hydrocortisone, Oregon Green 488, sodium fluorescein, and theophylline in 2-hydroxyethyl methacrylate/methacrylic acid (HEMA/MAA, pKa≈5.2) copolymer hydrogels as functions of composition, aqueous pH (2 and 7.4), and salinity. At pH 2, the hydrogels are nonionic, whereas at pH 7.4, hydrogels are anionic due to MAA ionization. Solute adsorption on and nonspecific electrostatic interaction with the polymer matrix are pronounced. To express deviation from ideal partitioning, we define an enhancement or exclusion factor, E ≡ k/φ1, where φ1 is hydrogel water volume fraction. All solutes exhibit E > 1 in 100 wt % HEMA hydrogels owing to strong specific adsorption to HEMA strands. For all solutes, E significantly decreases upon incorporation of anionic MAA into the hydrogel due to lack of adsorption onto charged MAA moieties. For dianionic sodium fluorescein and Oregon Green 488, and partially ionized monoanionic acetazolamide at pH 7.4, however, the decrease in E is more severe than that for similar-sized nonionic solutes. Conversely, at pH 2, E generally increases with addition of the nonionic MAA copolymer due to strong preferential adsorption to the uncharged carboxylic-acid group of MAA. For all cases, we quantitatively predict enhancement factors for the six drugs using only independently obtained parameters. In dilute solution for solute i, Ei is conveniently expressed as a product of individual enhancement factors for size exclusion (Ei(ex)), electrostatic interaction (Ei(el)), and specific adsorption (Ei(ad)):Ei≡Ei(ex)Ei(el)Ei(ad). To obtain the individual enhancement factors, we employ an extended Ogston mesh-size distribution for Ei(ex); Donnan equilibrium for Ei(el); and Henry's law characterizing specific adsorption to the polymer chains for Ei(ad). Predicted enhancement factors are in excellent agreement with experiment

A critical review of modeling transport phenomena in polymer-electrolyte fuel cells

Polymer-electrolyte fuel cells are a promising energy-conversion technology. Over the last several decades significant progress has been made in increasing their performance and durability, of which continuum-level modeling of the transport processes has played an integral part. In this review, we examine the state-of-the-art modeling approaches, with a goal of elucidating the knowledge gaps and needs going forward in the field. In particular, the focus is on multiphase flow, especially in terms of understanding interactions at interfaces, and catalyst layers with a focus on the impacts of ionomer thin-films and multiscale phenomena. Overall, we highlight where there is consensus in terms of modeling approaches as well as opportunities for further improvement and clarification, including identification of several critical areas for future research

Selection and optimization of piezoelectric polyvinylidene fluoride polymers for adaptive optics in space environments

Various piezoelectric polymers based on polyvinylidene fluoride (PVDF) are of interest for large aperture space-based telescopes. Dimensional adjustments of adaptive polymer films depend on charge deposition and require a detailed understanding of the piezoelectric material responses which are expected to deteriorate owing to strong vacuum UV, � -, X-ray, energetic particles and atomic oxygen exposure. We have investigated the degradation of PVDF and its copolymers under various stress environments detrimental to reliable operation in space. Initial radiation aging studies have shown complex material changes with lowered Curie temperatures, complex material changes with lowered melting points, morphological transformations and significant crosslinking, but little influence on piezoelectric d33 constants. Complex aging processes have also been observed in accelerated temperature environments inducing annealing phenomena and cyclic stresses. The results suggest that poling and chain orientation are negatively affected by radiation and temperature exposure. A framework for dealing with these complex material qualification issues and overall system survivability predictions in low earth orbit conditions has been established. It allows for improved material selection, feedback for manufacturing and processing, material optimization/stabilization strategies and provides guidance on any alternative materials