A colchicine-loaded nanoemulgel (COL-nEMG) was developed for rapid and potent topical therapy of acute gouty arthritis (AGA). An O/W COL-loaded nanoemulsion (COL-nEMS, 14.20 ± 1.73 nm) was first prepared and optimized step by step, including excipient screening, pseudo-ternary phase diagram, in vitro transdermal delivery and D-optimal design. The optimized COL-nEMS containing 10% isosorbide dimethyl ether (DMI) was then dispersed into a gel matrix to produce the final COL-loaded nanoemulgel (COL-nEMG-DMI10). COL-nEMG-DMI10 exhibited a homogeneous appearance, favorable rheological properties, stable three-dimensional porous structure, and good storage stability with a steady-state transdermal flux of 54.6 ± 3.7 µg/cm[2]/h and 8 h cumulative permeation amount of 425.6 ± 28.3 µg/cm[2]. In an AGA mouse model, COL-nEMG-DMI10 demonstrated rapid therapeutic effects with joint swelling inhibition rate (JSIR) of 37.0 ± 3.4% and maximum possible effect of 37.5 ± 5.3% at 1 h post-administration. In addition, COL-nEMG-DMI10 significantly suppressed the levels of local inflammatory cytokines, including TNF-α and IL-1β, in the ankle joints of AGA animals. This COL-nEMG-DMI10 topical formulation provides a promising treatment strategy for AGA with rapid and pronounced therapeutic efficacy.

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.

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.

In situ forming implants (ISFIs) have gained considerable attention over the past decade as minimally invasive long-acting injectable systems for localised and sustained drug delivery. N-Methyl-2-pyrrolidone (NMP) remains the most commonly used solvent for ISFIs; however, concerns regarding its environmental toxicity and teratogenicity have driven the search for alternatives. Therefore, in this study, we investigated bio-derived and bio-renewable solvents - dimethyl isosorbide (DMI) and γ-valerolactone (GVL) - as potential substitutes for NMP. ISFI formulations were individually prepared with each solvent and poly(lactic-co-glycolic acid) (PLGA; L/G 1:1, 10 kDa) at polymer concentrations of 20, 30, and 40% w/w, and containing 1% w/w eosin Y dye as a model hydrophilic drug. ISFIs were subsequently evaluated for their rheological behaviour, injectability, implant morphology, and dye and solvent release. Rheological analyses revealed solvent-dependent differences, with GVL exhibiting flow behaviour comparable to NMP, while DMI showed significantly higher viscosity. These trends translated into injectability performance. Post-injection, NMP- and DMI-based ISFIs formed spherical implants, whereas GVL-based ISFIs produced collapsed and irregular structures. Moreover, in vitro release studies of eosin Y showed that GVL-based ISFIs significantly reduced burst release while exhibiting overall faster release kinetics, which was attributed to rapid polymer solidification and collapsed implant morphology that shortened diffusion path lengths. A two-stage model was developed to fit the release profiles and determine the average diffusion coefficients (D), allowing a quantitative comparison of the different formulations. To compare the performance of the solvents in vivo in rats, ISFI formulations were prepared containing testosterone (2.5% w/w) as a clinically relevant hydrophobic drug. Testosterone release from DMI- and GVL-based ISFIs was comparable to NMP, although NMP formulations resulted in lower overall plasma concentrations. This study highlights the potential of DMI and GVL as alternative solvents for ISFIs, with comparable performance to the traditionally used NMP.

Cholesteric liquid crystal polymer network (CLCN) mirrors featuring a broad reflection band have attracted considerable interest for use in optical filters and decorative applications. To date, however, the development of mirrors with encryption capabilities remains unexplored. In this work, a series of chiral additives were synthesized from isosorbide and 4'-n-alkyl-(1,1'-biphenyl)-4-carboxylic acids. Using polymerization-induced chiral additive diffusion, we then prepared a set of CLCN films exhibiting broad reflection bands. By stacking these films with an optically clear adhesive, a broadband CLCN mirror with high reflectance was fabricated. Furthermore, a patterned half-wave plate was fabricated using a nematic liquid crystal polymer network (NLCN) in combination with a CLCN. A modified mirror was constructed by incorporating the patterned half-wave plate during the stacking process. When illuminated with circularly polarized light, this configuration revealed vivid colored images. These results demonstrate the potential of such mirrors for encryption purposes.

This study addresses a critical challenge in delivering a drug to prevent angina in the early morning hours, aligning with the heart's circadian rhythm. For this purpose, we formulated Isosorbide dinitrate (ISDN) - loaded spherules for delayed release (DR) followed by sustained release (SR) using ethyl cellulose by spheronization technique. DOE-led optimisation is done to develop the design of space for optimized spherules. The DR-coated spherules exhibit possible surface modifications, indicating the presence of a coating layer that can influence the release profile and provide marginally better flow characteristics (Angle of repose 31.38 ± 0.02, Carr's index 10 ± 0.35%, Hausner's Ratio 1.11 ± 0.037) compared to granules and SR spherules. In vitro drug release in pH 1.2 is 4.8% indicating negligible drug release due to DR coating, whereas, under colonic pH (7.4) conditions, initially 40% is released as a burst release and approximately 60% of ISDN is released over 24 h, which indicates that DR coating modifies the drug release profile. Following the successful modulation of release behaviour via engineering the delivery system, spherules coated with ethyl cellulose and Eudragit S-100 exhibit negligible release in pH 1.2, confirming strong resistance for release in the gastric environment. The design of space (DOS), optimized through JMP software using the Design of Experiments (DOE) approach, confirms the targeted performance. The results of the DOE to experimental validated results were within 5% deviation.

Safe and Sustainable by Design (SSbD) and life‑course exposome science share a primary‑prevention goal: reducing harmful exposures by intervening early in the chemical and product life cycle. Here we propose an integrated, replacement‑first decision workflow that links life‑course exposure considerations to SSbD stage‑gates using New Approach Methodologies (NAMs). The framework combines: (i) problem formulation informed by susceptible windows and populations; (ii) AOP‑guided selection and curation of mechanistic in vitro bioactivity evidence (e.g., ToxCast/Tox21, transcriptomics); (iii) physiologically based pharmacokinetic (PBPK) modelling with quantitative in vitro‑to‑in vivo extrapolation to translate in vitro potency into internal dose anchors; and (iv) transparent multi‑criteria synthesis to support early design trade‑offs. We illustrate this approach with an endocrine‑relevant substitution scenario comparing bisphenol A (BPA) with a structurally similar alternative (BPAP) and a bio‑based monomer candidate (isosorbide). Estrogen receptor (ER) bioactivity anchors derived from curated HTS assays are contrasted with PBPK‑predicted internal concentration ranges to generate an internal margin for stage‑gate decisions. The example shows how candidates with weak or absent pathway‑relevant bioactivity can be advanced, while structurally similar alternatives with ER potency approaching predicted internal concentrations can be deprioritised or redesigned pending improved exposure controls. By explicitly mapping NAM outputs to AOP key events and life‑course windows, the workflow operationalises the 3Rs by replacing broad exploratory animal testing with targeted, human‑relevant evidence and reducing unnecessary in vivo studies through early prioritisation.

The hazard identification of chemicals is a key step of the 'Safe and Sustainable by Design' (SSbD) framework introduced by the European Commission, aiming to eliminate hazardous substances early in innovation. In this context, in silico methods such as (Quantitative) Structure-Activity Relationship ((Q)SAR) models offer rapid, cost-effective, and animal-free alternatives for early-stage hazard screening. The Partnership for the Assessment of Risks from Chemicals (PARC) is developing a toolbox to facilitate SSbD assessments containing numerous (Q)SAR models. Challenges, however, exist in using and combining multiple in silico tools. Here, we developed a workflow to assess chemical hazards using multiple in silico tools within the PARC toolbox. The workflow consists of three phases: 1) the preparation stage, 2) running the models, and 3) the evaluation stage. To demonstrate the approach, we applied it to a case study comparing Bisphenol A, Isosorbide, and Bisphenol AP. Tools from the PARC toolbox were screened for relevance, transparency, and open access availability. Only models aligned with SSbD required endpoints and adequately documented via (Q)SAR Model Reporting Formats were retained. The properties assessed in this study cover carcinogenicity, germ cell mutagenicity, reproductive toxicity, endocrine disruption, persistence, bioaccumulation, and aquatic toxicity. Predictions were filtered using applicability domain criteria and reliability scores. Next, three strategies were applied for integrating different model outputs. Model agreement varied across endpoints and integration methods. This emphasizes the possibility of different SSbD assessment outcomes and thus the need for transparent documentation of the chosen strategy and explicit handling of uncertainty. Our study demonstrates how multiple models can systematically and transparently be integrated via the developed workflow. Key areas for improvement are to refine integration strategies, harmonize the definition and communication of applicability domains across tools, expand in silico coverage for currently underrepresented endpoints, and to develop approaches to consider data gaps in SSbD assessments.