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Background: The World Health Organization has identified Helicobacter pylori, a Gram‐negative bacterium responsible for several gastric disorders, as one of the pathogenic bacteria that requires newer non‐antibiotic approaches for its management. We previously demonstrated that nanostructured lipid carriers (NLC) loaded with docosahexaenoic acid (DHA‐NLC) have excellent in vitro performance against H. pylori. Materials and Methods: NLC were tested against different H. pylori strains and bacteria representative from human gut microbiota. For H. pylori, resistance development and membrane permeability assays were also performed. In vivo efficacy studies were done using an H. pylori‐infected mouse model. Microbiome analysis (16S rRNA sequencing analysis) was performed on mice feces before and after DHA‐NLC treatment. Results: NLC specifically killed different H. pylori strains by membrane disruption without inducing bacterial resistance. In vivo studies demonstrated that DHA‐NLC (2 mg/mL containing 50 μM of DHA) reduced 90%–95% of the H. pylori burden and eradicated infection in 50% of the animals when treatment was administrated ad libitum for 14 days. No significant differences were found between the administration procedure (ad libitum vs oral gavage). Also, increasing the DHA‐NLC concentration to 4 and 8 mg/mL did not translate into an improvement in antibacterial performance. Notably, gut microbiome analysis showed no alterations, highlighting the safety to the gut microbiota. Finally, no histopathological changes were reported (stomach/liver sections). Conclusions: Overall, our results emphasize DHA‐NLC as a promising approach for H. pylori infection management, since they can effectively reduce the H. pylori burden without affecting gut microbiota and, in opposition to antibiotics, without anticipating the development of resistance to this treatment. [ABSTRACT FROM AUTHOR]

Skin drug delivery is an emerging route in drug development, leading to an urgent need to understand the behaviour of active pharmaceutical ingredients within the skin. Given, As one of the body's first natural defences, the barrier properties of skin provide an obstacle to the successful outcome of any skin drug therapy. To elucidate the mechanisms underlying this barrier, reductionist strategies have designed several models with different levels of complexity, using non-biological and biological components. Besides the detail of information and resemblance to human skin in vivo, offered by each in vitro model, the technical and economic efforts involved must also be considered when selecting the most suitable model. This review provides an outline of the commonly used skin models, including healthy and diseased conditions, in-house developed and commercialized models, their advantages and limitations, and an overview of the new trends in skin-engineered models. [ABSTRACT FROM AUTHOR]

Xanthone derivatives have a dibenzo‐y‐pyrone scaffold which has gained great interest in Medicinal Chemistry due to their diverse biological activities. Usually, its synthesis requires multi‐step synthetic routes using harsh conditions and high catalyst loadings. In this communication, we report for the first time a one‐pot synthesis of the xanthone scaffold based on a carbonylative Suzuki coupling. Iodophenol and (2‐methoxyphenyl)boronic acid were coupled under carbon monoxide, generated from a carbon monoxide surrogate. An experimental data‐based model was built to guide the reaction optimization. The optimized conditions were 1 mol% of a pincer complex as palladium catalyst, 5 equivalents of K2CO3 as base, and DMF:water (7 : 3) as solvent. The robustness of the synthetic method, namely in terms of the reactants scope, was also evaluated. This approach provided the xanthone scaffold in high yields and provided a deep insight into the carbonylative Suzuki couplings. [ABSTRACT FROM AUTHOR]

Abstract: The low bioavailability and nonspecific distribution of dapsone and clofazimine, commonly applied in combination for the treatment of leprosy, can produce toxic effects. Nanotechnological approaches enhance the delivery of these drugs. Therefore, a high‐performance liquid chromatography method was developed for the simultaneous determination of dapsone and clofazimine loaded in nanoformulations for quality control purposes. Chromatographic separation was achieved on a reversed‐phase Kinetex core‐shell C18 column, followed by spectrophotometric detection at 280 nm. Considering the different physicochemical properties of dapsone and clofazimine, elution was performed in gradient mode using an aqueous acetate buffer (50 mmol/L, pH 4.8) and an increasing acetonitrile content from 27 to 63% v/v at a flow rate of 1.0 mL/min with retention times of 6.2 and 14.0 min, respectively. The method was validated according to the European Medicines Agency guideline and it was found to be specific, accurate (99.6–114.0%), and precise for intra‐ (RSD ≤ 1.8%) and interday assays (RSD ≤ 12.5%). Both drugs showed stability after 24 h at room temperature and over three freeze–thaw cycles with recoveries ≥86.2%. Low temperature (4°C) in the autosampler caused the precipitation of clofazimine and must be avoided. The validated method was successfully applied in the quantification of both drugs in nanoformulations. [ABSTRACT FROM AUTHOR]