Supramolecular Hydrogels Consisting of Nanofibers Increase the Bioavailability of Curcuminoids in Inflammatory Skin Diseases

The low bioavailability of curcuminoids (CCMoids) limits their use in the treatment of inflammatory skin diseases. Our work shows that this constraint can be overcome upon their incorporation into supramolecular hydrogels assembled from a gemini-imidazolium amphiphilic gelator. Three structural CCMoid analogues were used to prepare supramolecular hydrogels, and it was observed that the concentration of both the gelator and CCMoid and the proportion of solvents influence the self-assembly process. Moreover, the mechanical properties of the nanostructured gels were studied to find the optimum gels, which were then further characterized microscopically, and their ability to release the CCMoid was evaluated. The physicochemical properties of the CCMoids play a fundamental role in the interaction with the gelator, influencing not only the gelation but also the morphology at the microscopic level, the mechanical properties, and the biopharmaceutical behavior such as the amount of CCMoid released from the gels. The nanostructured supramolecular hydrogels, which contain the CCMoids at much lower concentrations (μg/mL) in comparison to other products, promote the penetration of the CCMoids within the skin, but not their transdermal permeation, thus preventing any possible systemic effects and representing a safer option for topical administration. As a result, the CCMoid-containing hydrogels can effectively reduce skin inflammation in vivo, proving that these supramolecular systems are excellent alternatives in the treatment of inflammatory skin diseases.This work was supported by the projects PID2020-115663GB-C3-2, PID2019-108794GB-I00, and PID2020–115631GB-I00 funded by MCIN/AEI/10.13039/501100011033 from the Ministerio de Ciencia e Innovación. We thank AGAUR for a grant to consolidated research groups 2017SGR1277. A.G.-C. and N.A.-A. acknowledge the financial support from the Spanish Ministry Science, through the “Severo Ochoa” Programme for Centres of Excellence (FUNFUTURE) (2020-2023). A.G.-C. also acknowledges a Ramon y Cajal Grant (RYC-2017-22910).With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).Peer reviewe

Metabolism of L-fucose and L-rhamnose in Escherichia coli: aerobic-anaerobic regulation of L-lactaldehyde dissimilation.

L-Lactaldehyde is a branching point in the metabolic pathway of L-fucose and L-rhamnose utilization. Under aerobic conditions, L-lactaldehyde is oxidized to L-lactate by the enzyme lactaldehyde dehydrogenase, while under anaerobic conditions, L-lactaldehyde is reduced to L-1,2-propanediol by the enzyme propanediol oxidoreductase. Aerobic growth on either of the methyl pentoses induces a lactaldehyde dehydrogenase enzyme which is inhibited by NADH and is very stable under anaerobic conditions. In the absence of oxygen, the cell shifts from the oxidation of L-lactaldehyde to its reduction, owing to both the induction of propanediol oxidoreductase activity and the decrease in the NAD/NADH ratio. The oxidation of L-lactaldehyde to L-lactate is again restored upon a change to aerobic conditions. In this case, only the NAD/NADH ratio may be invoked as a regulatory mechanism, since both enzymes remain active after this change. Experimental evidence in the presence of rhamnose with mutants unable to produce L-lactaldehyde and mutants capable of producing but not further metabolizing it points toward L-lactaldehyde as the effector molecule in the induction of lactaldehyde dehydrogenase. Analysis of a temperature-sensitive mutation affecting the synthesis of lactaldehyde dehydrogenase permitted us to locate an apparently single regulator gene linked to the ald locus at 31 min and probably acting as a positive control element on the expression of the structural gene

glc locus of Escherichia coli: characterization of genes encoding the subunits of glycolate oxidase and the glc regulator protein.

The locus glc (min 64.5), associated with the glycolate utilization trait in Escherichia coli, is known to contain glcB, encoding malate synthase G, and the gene(s) needed for glycolate oxidase activity. Subcloning, sequencing, insertion mutagenesis, and expression studies showed five additional genes: glcC and in the other direction glcD, glcE, glcF, and glcG followed by glcB. The gene glcC may encode the glc regulator protein. Consistently a chloramphenicol acetyltransferase insertion mutation abolished both glycolate oxidase and malate synthase G activities. The proteins encoded from glcD and glcE displayed similarity to several flavoenzymes, the one from glcF was found to be similar to iron-sulfur proteins, and that from glcG had no significant similarity to any group of proteins. The insertional mutation by a chloramphenicol acetyltransferase cassette in either glcD, glcE, or glcF abolished glycolate oxidase activity, indicating that presumably these proteins are subunits of this enzyme. No effect on glycolate metabolism was detected by insertional mutation in glcG. Northern (RNA) blot experiments showed constitutive expression of glcC but induced expression for the structural genes and provided no evidence for a single polycistronic transcript

Novel nanostructured lipid carriers loading Apigenin for anterior segment ocular pathologies

Dry eye disease (DED) is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction and constitutes one of the most common ocular conditions worldwide. However, its treatment remains unsatisfactory. While artificial tears are commonly used to moisturize the ocular surface, they do not address the underlying causes of DED. Apigenin (APG) is a natural product with anti-inflammatory properties, but its low solubility and bioavailability limit its efficacy. Therefore, a novel formulation of APG loaded into biodegradable and biocompatible nanoparticles (APG-NLC) was developed to overcome the restricted APG stability, improve its therapeutic efficacy, and prolong its retention time on the ocular surface by extending its release. APG-NLC optimization, characterization, biopharmaceutical properties and therapeutic efficacy were evaluated. The optimized APG-NLC exhibited an average particle size below 200 nm, a positive surface charge, and an encapsulation efficiency over 99 %. APG-NLC exhibited sustained release of APG, and stability studies demonstrated that the formulation retained its integrity for over 25 months. In vitro and in vivo ocular tolerance studies indicated that APG-NLC did not cause any irritation, rendering them suitable for ocular topical administration. Furthermore, APG-NLC showed non-toxicity in an epithelial corneal cell line and exhibited fast cell internalization. Therapeutic benefits were demonstrated using an in vivo model of DED, where APG-NLC effectively reversed DED by reducing ocular surface cellular damage and increasing tear volume. Anti-inflammatory assays in vivo also showcased its potential to treat and prevent ocular inflammation, particularly relevant in DED patients. Hence, APG-NLC represent a promising system for the treatment and prevention of DED and its associated inflammation.This research was supported by the Spanish Ministry of Science and Innovation (PID2021-122187NB-C32) and a Llavors project (LLAV 0004). EBS acknowledges FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/ 2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB. E.S.-L. acknowledges the support of Grants for the Requalification of the Spanish University System.Peer reviewe