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.

Unveiling the Ability of Witch Hazel (Hamamelis virginiana L.) Bark Extract to Impair Keratinocyte Inflammatory Cascade Typical of Atopic Eczema.

Hamamelis virginiana L. bark extract is a traditional remedy for skin affections, including atopic dermatitis/eczema (AD). Hamamelis preparations contain tannins, including hamamelitannin (HT), although their pharmacological role in AD is still unknown. This study aimed to study the rational for its topical use by considering the impact of crucial biomarkers on AD pathogenesis. A standardized extract (HVE) (0.5−125 µg/mL) was compared to hamamelitannin (HT), its main compound (0.5−5 µg/mL), in a model of human keratinocytes (HaCaTs), challenged with an AD-like cytokine milieu (TNF-α, IFN-γ, and IL-4). HVE inhibited the release of mediators involved in skin autoimmunity (IL-6 and IL-17C) and allergy (TSLP, IL-6, CCL26, and MMP-9) with a concentration-dependent fashion (IC50s < 25 µg/mL). The biological mechanism was ascribed, at least in part, to the impairment of the NF-κB-driven transcription. Moreover, HVE counteracted the proliferative effects of IL-4 and recovered K10, a marker of skin differentiation. Notably, HT showed activity on well-known targets of IL-4 pathway (CCL26, K10, cell proliferation). To the best of our knowledge, this work represents the first demonstration of the potential role of Hamamelis virginiana in the control of AD symptoms, such as itch and skin barrier impairment, supporting the relevance of the whole phytocomplex.

Anti-Inflammatory and Anti-Acne Effects of Hamamelis virginiana Bark in Human Keratinocytes.

Cutibacterium acnes (C. acnes) is recognized as one of the main triggers of the cutaneous inflammatory response in acne vulgaris, a chronic skin disorder with a multifactorial origin. Witch hazel (Hamamelis virginiana L.) is a plant widely used for skin inflammatory conditions, with some preliminary anti-inflammatory evidence on the skin, but lacking data on acne conditions. This study aimed to evaluate the effect of a glycolic extract from Hamamelis virginiana bark (HVE) versus C. acnes-induced inflammation in human keratinocytes (HaCaT). Phytochemical investigations of HVE identified hamamelitannin (HT) and proanthocyanidins as the most abundant compounds (respectively, 0.29% and 0.30% w/wextract). HVE inhibited C. acnes-induced IL-6 release (IC50: 136.90 µg/mL), by partially impairing NF-κB activation; however, no antibacterial or antibiofilm activities were found. In addition, HVE showed greater anti-inflammatory activity when TNF-α was used as a proinflammatory stimulus (IC50 of 38.93 µg/mL for IL-8 release), partially acting by antioxidant mechanisms, as shown for VEGF inhibition. The effects of HVE are primarily based on the proanthocyanidin content, as HT was found inactive on all the parameters tested. These results suggest further investigations of HVE in other inflammatory-based skin diseases.

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.