A Safe-by-Design Approach for the Synthesis of a Novel Cross-Linked Hyaluronic Acid with Improved Biological and Physical Properties.

Hyaluronic acid (HA) is a polymer with unique biological properties that has gained in interest over the years, with applications in pharmaceutical, cosmetic, and biomedical fields; however, its widespread use has been limited by its short half-life. Therefore, a new cross-linked hyaluronic acid was designed and characterized using a natural and safe cross-linking agent, such as arginine methyl ester, which provided improved resistance to enzymatic action, as compared to the corresponding linear polymer. The antibacterial profile of the new derivative was shown to be effective against S. aureus and P. acnes, making it a promising candidate for use in cosmetic formulations and skin applications. Its effect on S. pneumoniae, combined with its excellent tolerability profile on lung cells, also makes this new product suitable for applications involving the respiratory tract.

Activation of Vegetable Oils by Reaction with Maleic Anhydride as a Renewable Source in Chemical Processes: New Experimental and Computational NMR Evidence.

Vegetable oils are bio-based and sustainable starting materials that can be used to develop chemicals for industrial processes. In this study, the functionalization of three vegetable oils (grape, hemp, and linseed) with maleic anhydride was carried out either by conventional heating or microwave activation to obtain products that, after further reactions, can enhance the water dispersion of oils for industrial applications. To identify the most abundant derivatives formed, trans-3-octene, methyl oleate, and ethyl linoleate were reacted as reference systems. A detailed NMR study, supported by computational evidence, allowed for the identification of the species formed in the reaction of trans-3-octene with maleic anhydride. The signals in the 1H NMR spectra of the alkenyl succinic anhydride (ASA) moieties bound to the organic chains were clearly identified. The reactions achieved by conventional heating were carried out for 5 h at 200 °C, resulting in similar or lower amounts of ASA units/g of oil with respect to the reactions performed by microwave activation, which, however, induced a higher viscosity of the samples.

A rhabdomyosarcoma hydrogel model to unveil cell-extracellular matrix interactions.

Three-dimensional (3D) culture systems have progressively attracted attention given their potential to overcome limitations of classical 2D in vitro systems. Among different supports for 3D cell culture, hydrogels (HGs) offer important advantages such as tunable mechanical and biological properties. Here, a biocompatible hyaluronic acid-polyethylene glycol HG was developed to explore the pro-migratory behavior of alveolar rhabdomyosarcoma (ARMS) cells. Proteomic analysis of ARMS xenografts unveiled the composition of the extracellular matrix (ECM) elucidating the most representative proteins. In parallel, HGs were obtained by the combination of a thiol-containing hyaluronic acid derivative and different polyethylene glycol (PEG) dimaleimide polymers. The selection of the optimal HG for ARMS cell growth was made based on degradation time, swelling, and cell distribution. Rheology measures and mechanical properties were assessed in the presence or absence of ECM proteins (collagen type I and fibronectin), as well as viability tests and cell distribution analysis. The role of ITGA5, the receptor of fibronectin, in determining ARMS cell migration was validated in vitro upon ITGA5 silencing. In vivo, cell dissemination and the capacity for engrafting were validated after injecting ARMS cell populations enriched for the level of ITGA5 in zebrafish embryos. To study the interactions with ARMS-specific ECM proteins (HG + P), the key players from the Rho and heat-shock pathways were investigated by reverse phase protein array (RPPA). Our data suggest that the developed 3D ARMS model is useful for identifying potential physical hallmarks that allow cancer cells to resist therapy, escape from the immune-system and increase dissemination.

Design, Synthesis, Characterization, and In Vitro Evaluation of a New Cross-Linked Hyaluronic Acid for Pharmaceutical and Cosmetic Applications.

Hyaluronic acid (HA), an excellent biomaterial with unique bio properties, is currently one of the most interesting polymers for many biomedical and cosmetic applications. However, several of its potential benefits are limited as it is rapidly degraded by hyaluronidase enzymes. To improve the half-life and consequently increase performance, native HA has been modified through cross-linking reactions with a natural and biocompatible amino acid, Ornithine, to overcome the potential toxicity commonly associated with traditional linkers. 2-chloro-dimethoxy-1,3,5-triazine/4-methylmorpholine (CDMT/NMM) was used as an activating agent. The new product (HA-Orn) was extensively characterized to confirm the chemical modification, and rheological analysis showed a gel-like profile. In vitro degradation experiments showed an improved resistance profile against enzymatic digestions. Furthermore, in vitro cytotoxicity studies were performed on lung cell lines (Calu-3 and H441), which showed no cytotoxicity.

Evaluating Natural Alternatives to Synthetic Acrylic Polymers: Rheological and Texture Analyses of Polymeric Water Dispersions.

The natural cosmetics market is growing, in line with the interest of public opinion on environmental safety. The availability of polysaccharides for cosmetic use is very wide; each raw material has its own sensorial specificities and hardly matches the performance of synthetic polymers. We developed an instrumental protocol based on rheology and texture analysis to evaluate alternatives to acrylic polymers. The study has been carried out on a set of water dispersions prepared with different synthetic, semisynthetic, and natural polymers at different concentrations. Using statistical principal component analysis, three different clusters have been identified: group A includes polymers with a stringy viscoelastic behavior, group B includes polymers with low firmness and a weak-gel rheological pattern, and group C includes polymers which formed soft and elastic gels. This work showed that this instrumental approach is a powerful tool to comprehensively characterize new rheological modifiers and to forecast their contribution to the formulation based on their applicative features. Moreover, rheology and texture analysis turned out to be complementary tools useful to compare polymeric raw materials and to identify appropriate alternatives to synthetic ones in order to formulate green cosmetic products.