Improved Dermal and Transdermal Delivery of Curcumin with SmartFilms and Nanocrystals

Poor aqueous solubility of active compounds is a major issue in today’s drug delivery. In this study the smartFilm-technology was exploited to improve the dermal penetration efficacy of a poorly soluble active compound (curcumin). Results were compared to the dermal penetration efficacy of curcumin from curcumin bulk suspensions and nanocrystals, respectively. The smartFilms enabled an effective dermal and transdermal penetration of curcumin, whereas curcumin bulk- and nanosuspensions were less efficient when the curcumin content was similar to the curcumin content in the smartFilms. Interestingly, it was found that increasing numbers of curcumin particles within the suspensions increased the passive dermal penetration of curcumin. The effect is caused by an aqueous meniscus that is created between particle and skin if the dispersion medium evaporates. The connecting liquid meniscus causes a local swelling of the stratum corneum and maintains a high local concentration gradient between drug particles and skin. Thus, leading to a high local passive dermal penetration of curcumin. The findings suggest a new dermal penetration mechanism for active compounds from nano-particulate drug delivery systems, which can be the base for the development of topical drug products with improved penetration efficacy in the future.     

Thiazole Analogues of the Marine Alkaloid Nortopsentin as Inhibitors of Bacterial Biofilm Formation

Anti-virulence strategy is currently considered a promising approach to overcome the global threat of the antibiotic resistance. Among different bacterial virulence factors, the biofilm formation is recognized as one of the most relevant. Considering the high and growing percentage of multi-drug resistant infections that are biofilm-mediated, new therapeutic agents capable of counteracting the formation of biofilms are urgently required. In this scenario, a new series of 18 thiazole derivatives was efficiently synthesized and evaluated for its ability to inhibit biofilm formation against the Gram-positive bacterial reference strains Staphylococcus aureus ATCC 25923 and S. aureus ATCC 6538 and the Gram-negative strain Pseudomonas aeruginosa ATCC 15442. Most of the new compounds showed a marked selectivity against the Gram-positive strains. Remarkably, five compounds exhibited BIC₅₀ values against S. aureus ATCC 25923 ranging from 1.0 to 9.1 µM. The new compounds, affecting the biofilm formation without any interference on microbial growth, can be considered promising lead compounds for the development of a new class of anti-virulence agents.     

Water-in-Oil-in-Water Nanoemulsions Containing Temulawak (Curcuma xanthorriza Roxb) and Red Dragon Fruit (Hylocereus polyrhizus) Extracts

Hydrophobic curcumin in temulawak extract and hydrophilic betacyanin in red dragon fruit extract are high-value bioactive compounds with extensive applications in functional food. In this study, these extracts were encapsulated in water-in-oil-in-water (w/o/w) nanoemulsions as a delivery system using a two-step high-energy emulsification method. PGPR and Span 20 were used as lipophilic emulsifiers for the primary w/o emulsion. The most stable w/o/w formulation with the least oil phase separation of 5% v/v consisted of w/o emulsion (15% w/w) and Tween 80 (1.5% w/w) as hydrophilic emulsifier. The formulation was characterized by a 189-nm mean droplet diameter, 0.16 polydispersity index, and –32 mV zeta potential. The freeze–thaw stability may be attributed to the combination of low w/o emulsion content and high Tween 80 concentration in the outer water phase of the w/o/w nanoemulsions used in this study. The IC₅₀ values of the nanoemulsion and the red dragon fruit extract were similar. It means that the higher concentration of curcumin in the nanoemulsions and the lower IC₅₀ value of temulawak extract ensured sufficient antioxidant activities of the w/o/w nanoemulsions.     

Synthesis,characterization and biological activity evaluation of new 3- methyl and 4- fluoro isoindoline-1, 3-dione/phthalimide analogues

The convenient route for the synthesis of a series of new Isoindoline-1, 3-dione/phthalimide analogues by condensation of substituted phthalic anhydride with an appropriate Ar-amine is described. Selective phthalimide derivatives were evaluated for their preliminary biological activities against Gram-positive, Gram-negative and fungi strains. These encouraging results could be helpful for the development of new antibacterial or antifungal agents.     

Using Terpene Synthase Plasticity in Catalysis: On the Enzymatic Conversion of Synthetic Farnesyl Diphosphate Analogues

Four synthetic farnesyl diphosphate analogues were enzymatically converted with three bacterial sesquiterpene synthases, including β-himachalene synthase (HcS) and (Z)-γ-bisabolene synthase (BbS) from Cryptosporangium arvum, and germacrene A synthase (SmTS6) from Streptomyces mobaraensis. These enzyme reactions not only yielded several previously unknown compounds, showing that this approach opened the door to a new chemical space, but substrates with blocked or altered reactivities also gave interesting insights into the cyclisation mechanisms and the potential to catalyse reactions with different initial cyclisation modes.     

Imaging the Magnetic Reversal of Isolated and Organized Molecular‐Based Nanoparticles using Magnetic Force Microscopy

In the race towards miniaturization in nanoelectronics, magnetic nanoparticles (MNPs) have emerged as potential candidates for their integration in ultrahigh‐density recording media. Molecular‐based materials open the possibility to design new tailor‐made MNPs with variable composition and sizes, which benefit from the intrinsic properties of these materials. Before their implementation in real devices is reached, a precise organization on surfaces and a reliable characterization and manipulation of their individual magnetic behavior are required. In this paper, it is demonstrated how molecular‐based MNPs are accurately organized on surfaces and how the magnetic properties of the individual MNPs are detected and tuned by means of low‐temperature magnetic force microscopy (LT‐MFM) with variable magnetic field. The magnetization reversal on isolated and organized MNPs is investigated; in addition, the temperature dependence of their magnetic response is evaluated.     

Highly Efficient Electrocatalysts for Oxygen Reduction Based on 2D Covalent Organic Polymers Complexed with Non‐precious Metals

A class of 2D covalent organic polymers (COPs) incorporating a metal (such as Fe, Co, Mn) with precisely controlled locations of nitrogen heteroatoms and holes were synthesized from various N‐containing metal–organic complexes (for example, metal–porphyrin complexes) by a nickel‐catalyzed Yamamoto reaction. Subsequent carbonization of the metal‐incorporated COPs led to the formation of COP‐derived graphene analogues, which acted as efficient electrocatalysts for oxygen reduction in both alkaline and acid media with a good stability and free from any methanol‐crossover/CO‐poisoning effects.     

A 3D 12‐Ring Zeolite with Ordered 4‐Ring Vacancies Occupied by (H2O)2 Dimers

A germanate zeolite, PKU‐14, with a three‐ dimensional large‐pore channel system was structurally characterized by a combination of high‐resolution powder X‐ray diffraction, rotation electron diffraction, NMR, and IR spectroscopy. Ordered Ge₄O₄ vacancies inside the [4⁶.6¹²] cages has been found in PKU‐14, in which a unique (H₂O)₂ dimer was located at the vacancies and played a structure‐directing role. It is the first time that water clusters are found to be templates for ordered framework vacancies.     

“Click” Chemistry Mildly Stabilizes Bifunctional Gold Nanoparticles for Sensing and Catalysis

A large family of bifunctional 1,2,3‐triazole derivatives that contain both a polyethylene glycol (PEG) chain and another functional fragment (e.g., a polymer, dendron, alcohol, carboxylic acid, allyl, fluorescence dye, redox‐robust metal complex, or a β‐cyclodextrin unit) has been synthesized by facile “click” chemistry and mildly coordinated to nanogold particles, thus providing stable water‐soluble gold nanoparticles (AuNPs) in the size range 3.0–11.2 nm with various properties and applications. In particular, the sensing properties of these AuNPs are illustrated through the detection of an analogue of a warfare agent (i.e., sulfur mustard) by means of a fluorescence “turn‐on” assay, and the catalytic activity of the smallest triazole–AuNPs (core of 3.0 nm) is excellent for the reduction of 4‐nitrophenol in water.     

Improving Site‐Directed RNA Editing In Vitro and in Cell Culture by Chemical Modification of the GuideRNA

Adenosine‐to‐inosine deamination can be re‐addressed to user‐defined mRNAs by applying phosphothioate/2′‐methoxy‐modified guideRNAs. Dense chemical modification of the guideRNA clearly improves performance of the covalent conjugates inside the living cell. Furthermore, careful positioning of a few modifications controls editing selectivity in vitro and was exploited for the challenging repair of the Factor 5 Leiden missense mutation.