Search Results (94)

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease characterized by epidermal barrier dysfunction, immune dysregulation, microbial imbalance, and severe pruritus. Emerging evidence establishes that barrier disruption is a central pathogenic driver capable of initiating inflammatory signaling, neuroimmune activation, and chronic disease instability. This understanding has shifted therapeutic paradigms toward barrier-directed strategies aimed at restoring epidermal resilience. This narrative review evaluates the mechanistic and clinical evidence surrounding isosorbide fatty acid diester molecules—specifically isosorbide dicaprylate (IDC) and isosorbide di-(linoleate/oleate) (IDL)—as a barrier-first approach for AD management. Early in vitro and ex vivo investigations demonstrated that IDC significantly improves epidermal hydration, transepidermal water loss, and the expression of barrier-associated genes linked to epidermal integrity. Subsequent studies showed that IDL expands these effects through coordinated regulation of keratinocyte differentiation, lipid homeostasis, and inflammatory stress pathways. Furthermore, recent mechanistic data highlight synergistic anti-inflammatory and pruritus-modulating effects involving TRPA1-, TRPV3-, and TSLP-associated pathways, while preserving tissue integrity under cytokine-induced stress. Clinically, these findings are supported by randomized studies in pediatric and adult cohorts demonstrating significant reductions in pruritus, favorable Eczema Area and Severity Index (EASI) responses, decreased topical corticosteroid dependence, and a reduction in the relative abundance of Staphylococcus aureus. Collectively, these findings support a barrier-first therapeutic framework in which restoration of epidermal resilience may beneficially influence multiple interconnected pathways involved in atopic dermatitis. Full article

Objectives: The aim of this study was to determine whether direct evidence shows that contemporary guideline-directed heart failure (HF) pharmacotherapies influence cardiac remodeling through hydrogen sulfide (H₂S) signaling, and to define the resulting evidence gap. Design: A systematic review was conducted according to PRISMA 2020. Registration: PROSPERO CRD420251238589. Data Sources: MEDLINE (PubMed), Web of Science, Scopus, and the Cochrane Library; searches were initiated in March 2025, covered publications from January 2007 onward, and were last updated in November 2025. Eligibility Criteria: Primary studies had to include (A) an HF or cardiac-remodeling model, (B) an HF-relevant pharmacological intervention, (C) direct assessment or manipulation of H₂S biology, and (D) at least one cardiac-remodeling endpoint. Results: Of the 40,796 unique records screened, 50 reports underwent full-text assessment and 14 unique studies were included. No study demonstrated that the remodeling benefits of ACE inhibitors, ARBs, ARNIs, beta-blockers, MRAs, hydralazine/isosorbide dinitrate, or SGLT2 inhibitors are mediated by endogenous H₂S signaling. Doiron et al. evaluated empagliflozin with or without the H₂S donor SG1002 in experimental HFpEF; the combination improved several outcomes beyond empagliflozin alone, but this adjunctive design does not establish H₂S mediation of empagliflozin action. Most eligible evidence concerned exogenous H₂S donors in animal models and reported improvements in fibrosis, hypertrophy, oxidative stress, mitochondrial injury, and cardiac function. The overall certainty was low because of preclinical predominance, heterogeneous models and H₂S assays, donor-specific pharmacology, and incompletely reported randomization and blinding. Conclusions: The principal finding is negative but clinically important: direct evidence that H₂S mediates established HF pharmacotherapy is currently absent. H₂S remains a promising experimental therapeutic candidate rather than an established shared mechanism or clinically validated treatment target. Full article

Trimethylsilyl ethers of monoprotected isosorbide derivatives have been subjected to multicomponent Hosomi–Sakurai reactions with allyl trimethylsilane and various aldehydes (aromatic or aliphatic) under the catalysis of trimethylsilyl triflate. This study has allowed for establishing that: (a) the best results are obtained in reactions involving TMS ethers of the endo-OH group; (b) the most suited protecting group is the tert-butyldiphenylsilyl ether. With this ideal substrate, a scope was studied using both aromatic and aliphatic aldehydes. Good yields and excellent diastereoselectivities were typically achieved with aromatic aldehydes, unless they were very encumbered at the ortho position or strongly electron-poor. With simple aliphatic enolizable aldehydes, it may be useful to use an excess of aldehydes because of self-condensation processes. These results open the way to conjugates of bio-based isosorbide with aldehyde-derived fragments, joined through a very stable ether group. Full article

To address the global water crisis, desalination technologies contribute about 1% of the global freshwater supply. Membrane-based desalination technologies offer high performance, operational ease, cost-effectiveness and high scalability compared to conventional thermal desalination modes. Among all membrane-based technologies, reverse osmosis is prevailing globally. However, the high energy demand of the reverse osmosis process and fouling in case of hypersaline feed streams motivate the exploration of alternative technologies, i.e., pervaporation. Pervaporation desalination involves dense hydrophilic polymer membranes to deal with high salt streams at low cost, along with less fouling than a few other membrane processes, i.e., reverse osmosis and membrane distillation. Mass transport through pervaporation desalination membranes is well-explained by solution-diffusion theory involving a tri-stage transfer, i.e., sorption, diffusion and evaporation. Since the last few decades, a green approach in all domains has offered chemical products and processes with the least hazards and minimal waste production. Application of biodegradable materials like poly(lactic acid) in combination with suitable green solvents, e.g., ethyl lactate, methyl lactate, cyrene, dimethyl isosorbide and gamma valerolactone for pervaporation desalination would be a good roadmap to meet the sustainability criterion. Some intrinsic features of poly(lactic acid) that make it a ‘material of choice’ for pervaporation desalination include hydrophilicity imparted by the presence of polar ester groups, high salt rejection, biodegradability with simple mineralization products, i.e., H₂O and CO₂, sustainable production, low toxicity, low carbon footprint, ease of processing and versatility. Poly(lactic acid) undergoes four interrelated degradation mechanisms: hydrolytic degradation, biodegradation, thermal degradation and photodegradation. The concern for poly(lactic acid) based pervaporation desalination is increased hydrolytic cleavage of poly(lactic acid) at high temperatures, which requires some modifications, e.g., nanoenhancement, additions of crosslinkers, surface modifications, addition of other polymers to prepare blends and post-treatments. These modifying strategies result in an increased stability and better performance of poly(lactic acid) films. However, optimization of various parameters relevant to such modifications leaves room for further research. This review offers a critical analysis of the need for biodegradable polymers with special focus on poly(lactic acid) rather than their fossil fuel-based alternatives, the environmental and health effects of all these polymers, cost estimation and possible performance-efficient, green and eco-friendly solutions. Full article

The effectiveness of poly(isosorbide carbonate) (PIC)—a bio-based polycarbonate synthesized from isosorbide (ISB)—degradation products in complex soil environments remains unverified. In the present study, the agricultural potential of PIC ammonolysis products—comprising urea and ISB—as a nitrogen (N) fertilizer was evaluated in a soil system. A pot experiment was conducted using komatsuna (Brassica rapa var. perviridis) to compare PIC degradation products with commercial urea, a urea and ISB mixture, and a no-N control. Application of PIC degradation products significantly enhanced plant growth, yielding fresh weight and N uptake comparable to those associated with commercial urea. The calculated N recovery efficiency for the PIC degradation products was 50%, falling within the typical range (30–60%) for inorganic fertilizers. Contrary to previous in vitro study results, ISB exhibited no significant biostimulant effect in the soil environment, likely owing to rapid microbial degradation. These findings serve as a preliminary proof-of-concept that PIC degradation products are a highly effective and bioavailable N source. Overall, the results suggest that if scaled appropriately, PIC ammonolysis products could contribute to circular use pathways for this specific plastic. Nonetheless, further studies across a broader range of crops and soils are required to confirm the generalizability of these results. Full article

Background/Objectives: Topical application of isosorbide diesters (IDEAS) derived from coconut and sunflower seed oil improve atopic dermatitis (AD) and reduce topical steroid use in adults. This randomized, double-blind, vehicle-controlled trial evaluates topical IDEAS (isosorbide diesters) with colloidal oatmeal for pediatric AD. Methods: Subjects aged 2–17 with mild to moderate AD applied either colloidal oatmeal cream or colloidal oatmeal cream with IDEAS daily. Hydrocortisone 2.5% was used as needed. AD severity, itch, sleep, steroid use, and microbiome data were collected at baseline, week 4, and week 8. Results: More participants in the IDEAS group compared to the control group achieved EASI 50 (81.0% vs. 56.3%, p = 0.10) and EASI 75 (42.9% vs. 18.8%, p = 0.12) and achieved a 4-point reduction in subjective itch at week 4 (45.5% vs. 6.3%, p = 0.0085) and week 8 (42.9% vs. 12.5%, p = 0.045). Use of topical steroids was lower in the IDEAS group (3.4 g vs. 13.3 g, p = 0.012) and the relative abundance of Staphylococcus aureus was reduced after 8 weeks. Conclusions: The addition of IDEAS to colloidal lotion improved AD, improved itch, reduced the use of topical steroids, and reduced the relative abundance of S. aureus in the skin microbiome. Full article

Isosorbide-based polycarbonate (PIC) shows promising applications in medical devices and food packaging, owing to its excellent thermal stability, biosafety, optical properties, and scratch resistance. However, trace impurities, especially formic acid in isosorbide (ISB), can significantly influence the performance of PIC. Crude ISB was purified via ion exchange resin. Furthermore, the chromatographic parameters and the adsorption kinetics of formic acid were investigated. The results show that adsorption of formic acid follows the pseudo-second-order kinetic model, suggesting that it is chemisorption. The performance of PIC synthesized from purified ISB has been improved significantly, exhibiting number-average molecular weight (M_n) of 53.9 kg/mol, elongation at break of 10.2%, and Young’s modulus of 1.84 GPa, along with notably enhanced thermal and optical properties. Full article

Isosorbide-based aliphatic polyesters are a promising class of biodegradable polymers for biomedical applications, representing an attractive alternative to poly(α-hydroxy acids). Derived from the bio-based bicyclic diol, they combine structural rigidity, tunable hydrophilicity, and enhanced biocompatibility, making them suitable for drug delivery and sustainable medical devices. In this study, we developed novel in situ forming implant (ISFI) formulations composed of poly(isosorbide sebacate) (PISEB) and dimethyl isosorbide (DMI), and evaluated their applicability for local delivery of doxycycline hyclate (DOXY), minocycline hydrochloride (MIN), and/or eugenol (EUG). Basic characteristics of new ISFI formulations were investigated. Rheological analysis demonstrated that the liquid formulations exhibited shear-thinning behavior, which is advantageous for ISFI systems. However, the MIN-loaded formulation exhibited excessively rapid drug release, with a pronounced initial burst (86.4 ± 5.9%) within 24 h, whereas the DOXY-loaded system showed a lower burst of 41.1 ± 5.9% over the same period. The effect of EUG addition on depot morphology and antibiotic release profiles was also assessed. In vitro drug release studies demonstrated that EUG reduced the release rate of both antibiotics, increasing and prolonging their antibacterial activity. Eugenol co-released with antibiotics also reduced the pro-inflammatory effect of the released antibiotic doses by more than tenfold. Full article

Isosorbide fatty acid diesters constitute a novel class of bioactive compounds with emerging therapeutic applications in inflammatory and barrier-compromised disorders. Among them, isosorbide dicaprylate (IDC) and isosorbide di-linoleate/oleate (IDL) synergistically strengthen epidermal barrier integrity, enhance stratum corneum hydration, regulate keratinocyte differentiation, suppress proinflammatory signaling, and beneficially modulate the skin microbiome. Randomized, double-blind clinical trials in both pediatric and adult populations with atopic dermatitis (AD) demonstrate that topical IDC + IDL formulations significantly reduce pruritus, corticosteroid dependence, and Staphylococcus aureus colonization while improving sleep quality, disease severity scores, and overall quality of life. Extending applications within and even beyond dermatology, isosorbide dimethyl fumarate (IDMF)—a next-generation fumarate derivative designed to mitigate sensitization risk—exhibits potent anti-inflammatory and antioxidant activities through NRF2 activation and NF-κB/IRF1 suppression. Preclinical studies in psoriasis and neuroinflammatory models, including multiple sclerosis, reveal robust modulation of oxidative stress and immune pathways with improved safety and mechanistic precision compared to conventional fumarates, although its systemic use remains exploratory and requires clinical validation. Collectively, isosorbide diesters emerge as multifunctional therapeutic agents offering barrier repair, immune modulation, and inflammation control, representing promising alternatives to corticosteroids and systemic immunosuppressants across dermatologic and systemic inflammatory disorders. Full article

The mechanical, thermal, physicochemical and structural properties of a thermoplastic cassava starch obtained by a twin-screw extrusion process were evaluated, using glycerol and isosorbide as plasticizers at different concentrations (30, 35 and 40% by weight) and storage times (1, 15 and 30 days) under controlled conditions of relative humidity of 47 ± 2% and temperature of 25 ± 2 °C. The results obtained show a decrease in tensile strength and modulus of elasticity and an increase in elongation in the initial measurements, suggesting that, in both cases, a plasticization phenomenon via absorption of humidity predominated in short times, while at prolonged times, a rigidification of the material occurred due to the generation of a retrogradation process. Likewise, a higher tensile strength and lower elongation were found in the materials plasticized with isosorbide. Finally, it was observed that the retrogradation phenomenon was more evident in the thermoplastic starch samples made with glycerol, and that the starches plasticized with isosorbide had lower moisture absorption, higher crystallinity and a predominantly Eh-type crystalline pattern, related to greater stability over time. Full article

Background/Objectives: Polysorbate 80 (PS80), a complex surfactant mixture, is widely recognized for its ability to enhance drug permeation across the blood–brain barrier (BBB). While this effect is generally attributed to the combined actions of its components, the specific contribution and potential selectivity of individual minor components remain poorly understood. This study therefore aimed to isolate and compare the primary minor components of PS80 to determine whether they uniformly enhance BBB permeation or exhibit drug-specific functions. Methods: In this research, four primary minor components of PS80—polyoxyethylene sorbitan monooleate (PSM), polyoxyethylene isosorbide monooleate (PIM), polyoxyethylene sorbitan dioleate (PSD), and a polyethylene glycol/polyoxyethylene sorbitan/polyoxyethylene isosorbide mixture (PEG/PS/PI mixture)—were isolated using preparative liquid-phase chromatography. Drug-loaded formulations were then prepared using the solvent evaporation method incorporating five model drugs: 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR, MW = 1013.39 Da), donepezil (MW = 379.49 Da), nimodipine (MW = 418.44 Da), chlorogenic acid (MW = 354.31 Da), and paclitaxel (MW = 853.92 Da). The permeability of these formulations across the BBB was evaluated in BALB/c mice after intravenous administration. Brain distribution of the lipophilic dye DiR was assessed using fluorescence imaging, whereas brain homogenate concentrations of therapeutic drugs were quantified by UPLC-MS/MS. Results: Results revealed that the enhancement of brain delivery was dependent on both the specific minor component and the drug. The PEG/PS/PI mixture specially enhanced the brain homogenate concentration of donepezil to 11.8 ± 1.2 ng/mL, representing a 6.9-fold enhancement, while PIM micelles increased the delivery of DiR, donepezil, and nimodipine. In contrast, PSM and PSD micelles improved transport of only DiR and donepezil. The broad performance of PIM suggests a more flexible formulation—a hypothesis that warrants further validation. Conversely, none of the different minor components enhanced the delivery of chlorogenic acid or paclitaxel, underscoring the critical role of specific drug–component interactions. Conclusions: This component-resolved insight challenges the conventional perception of PS80 and provides a rational framework for engineering precision brain-targeted delivery systems by selecting functional minor components. Full article

Skin hydration is fundamental for maintaining epidermal barrier integrity and overall skin homeostasis. Beyond traditional moisturizing agents, recent research has highlighted the role of aquaporins (AQPs), transmembrane water channels, in regulating epidermal hydration, barrier function, and cellular signalling. Among them, aquaporin-3 (AQP3), predominantly expressed in keratinocytes, has attracted particular attention due to its involvement in water and glycerol transport. Dysregulation of AQP expression has been associated with impaired barrier function, inflammatory skin disorders, and ageing. Growing evidence suggests that specific cosmetic ingredients and bioactive compounds, including glycerol, glyceryl glucoside, isosorbide dicaprylate, urea, retinoids, bakuchiol, peptides, plant extracts, and bacterial ferments, can modulate AQP3 expression, thereby improving skin hydration and resilience. Despite promising in vitro data, clinical evidence remains limited, mainly due to methodological and ethical constraints associated with assessing aquaporin expression in vivo. Nonetheless, aquaporins represent promising molecular targets for innovative cosmetic strategies aimed at enhancing hydration, promoting regeneration, and counteracting photoageing. Furthermore, AQP modulation may improve dermal delivery of active substances, providing new perspectives for advanced skincare formulation design. While the available evidence supports their cosmetic potential, emerging discussions on the safety of long-term AQP upregulation highlight the need for continued research and careful evaluation of such ingredients. Future studies should focus on elucidating the molecular mechanisms underlying AQP regulation and validating these findings in human clinical models. Full article

This paper presents a study of the thermal and rheological properties of isosorbide, showing that its degradation temperature (around 100 °C) is much lower than values previously proposed in the literature. Furthermore, remarkable calorimetric and viscoelastic behaviors, with features usually observed in semi-crystalline systems are presented. The onset of the melting is measured at 45 °C, while a glass transition occurs at −45 °C, followed by cold crystallization. Wide-angle X-ray diffraction confirmed the coexistence of crystalline domains and an amorphous fraction, which behaves as a molecular glass, with an estimated crystallinity of approximately 70%. Thermogravimetric analyses conducted under both air and nitrogen and at multiple heating rates, in line with ICTAC recommendations, established the robustness of the 100 °C degradation onset. These findings provide new structure–property relationships for isosorbide and open up new avenues for further research and development in this area. Full article

We investigated the practical adhesion of a conventional poly(vinyl alcohol) glue with a glassy isosorbide-based polycarbonate (ISB-PC) comprising isosorbide and 1,4-cyclohexanedimethanol. The addition of 1 wt.% of a copolymer of vinyl alcohol and butenediol to the ISB-PC greatly improved its lap-shear strength. This improvement may be attributed to the dissolution of the copolymer chains in the ISB-PC, which had a low water droplet contact angle. Furthermore, the blend was transparent because most of the copolymer chains dissolved in the ISB-PC. Microplastics present a serious environmental issue, even for adhesives. Therefore, the present technique to modify ISB-PC to show good lap-shear strength with a biodegradable glue is attractive. Full article

The increasing environmental concerns and regulatory restrictions on toxic conventional solvents have driven the search for sustainable alternatives. Dimethyl isosorbide (DMI), a bio-renewable solvent, has shown potential as a replacement for short-chain glycol ethers, although its use as solvent in liquid chromatography (LC) is underexplored. This study presents a physicochemical characterization of DMI with a particular focus on its application as an innovative solvent in LC analyses. The partition coefficient (log P = −0.44) was determined using the OECD 107 method, and viscosity measurements for DMI and its mixtures with water and ethanol were conducted at 25 °C, 40 °C, and 60 °C. Viscosity ranged from 1.28 mPa·s at 60 °C to 2.62 mPa·s at 40 °C. The Central Composite Face 2³ experimental design for studying the chromatographic behavior of DMI confirmed that 50% (v/v) DMI can be effectively utilized in the mobile phases, at a column temperature of 40 °C, with backpressures ranging from 160 to 300 bar and a UV cut-off at 240 nm. Its effectiveness as an eluent in LC was demonstrated for the quantification of methylparaben and propylparaben in pharmaceutical formulations. This study highlights DMI’s promise as a sustainable bio-renewable alternative to conventional organic solvents used as eluents in LC, supporting eco-friendly practices in pharmaceutical analysis. Full article