Modern drug carrier technologies, such as microemulsions with small droplet sizes and high surface areas, improve the ability of low water solubility active ingredients to permeate and localize. The goal of this study was to create microemulsion formulations for wound healing that contained both fusidic acid (FA), an antibacterial agent, and benzocaine (BNZ), a local anesthetic. Studies on characterization were carried out, including viscosity, droplet size, and zeta potential. The drug-loaded microemulsion had a stable structure with –3.014 ± 1.265 mV of zeta potential and 19.388 ± 0.480 nm of droplet size. In both in vitro release and ex vivo permeability studies, the microemulsion was compared with Fucidin cream and oily BNZ solution. According to the drug release studies, BNZ release from the microemulsion and the BNZ solution showed a similar profile (p > 0.05), while FA release from the microemulsion had a higher drug release compared to Fucidin cream (p < 0.001). The microemulsion presented lower drug permeation (p > 0.05) for both active ingredients, on the other hand, provided higher drug accumulation compared to the control preparations. Moreover, according to the results of in vitro wound healing activity, the microemulsion indicated a dose-dependent wound healing potential with the highest wound healing activity at the highest concentrations. To the best of our knowledge, this developed BNZ- and FA-loaded microemulsion would be a promising candidate to create new opportunities for wound healing thanks to present the active ingredients, which have low water solubility, in a single formulation and achieved higher accumulation than control preparations. Graphical Abstract

This study aimed to develop in situ gel formulations containing vanillic acid to enhance patient compliance and accelerate wound healing. Vanillic acid-loaded in situ gels were prepared and their physicochemical properties were evaluated through in vitro release and ex vivo permeation studies. Additionally, antioxidant capacity, cytotoxicity, wound healing, prostaglandin E2 levels, IL-6 inhibition and skin irritation tests were conducted. The optimized IN3-VA formulation exhibited a gelling temperature of 32.394 ± 0.842, a pH value of 4.780 ± 0.010 and a viscosity of 2473.33 ± 11.54 cP. It demonstrated specific mechanical properties, including hardness of 27.94 ± 1.30 g and adhesiveness of -97.00 ± 14.60 g.mm. The IN15-VA formulation showed improved parameters, with a hardness of 38.84 ± 3.33 g, adhesiveness of -126.35 ± 22.78 g.mm, pH value of 4.870 ± 0.010, viscosity of 3853.33 ± 30.55 cP and a gelling temperature of 31.854 ± 0.345. Both formulations demonstrated sustained release behavior, releasing 60% of the medication in vitro over 6 hours with no cytotoxic effects. They also decreased copper ion reduction and the release of nitric oxide, with cellular proliferation rates of 63% for IN3-VA and 73% for IN15-VA. Moreover, IN15-VA significantly reduced prostaglandin E2 levels, controlled IL-6 increase and exhibited non-irritating properties. The results suggest that these vanillic acid-loaded in situ gels hold promising potential in wound treatment due to their sustained release over 48 hours.

Hypericum species are known for their phytochemical richness and diverse pharmacological activities; however, the biological potential and underlying mechanisms of Hypericum triquetrifolium remain unclear. This study aimed to investigate the phytochemical profile and bioactivities of Hypericum triquetrifolium hydroalcoholic extract (HTE). Plant samples collected from Gelibolu (Çanakkale, Türkiye) were analyzed by HPTLC, revealing the presence of rutin, hyperoside, chlorogenic acid, neochlorogenic acid, and hypericin. Antioxidant activity was evaluated using DPPH, CUPRAC, and FRAP assays, demonstrating strong activity across all tests. Anti-inflammatory effects were assessed in LPS-stimulated RAW264.7 macrophages. HTE significantly reduced nitrite, PGE₂, IL-6, ROS, and MDA levels, with the most pronounced effect observed at 0.5 mg/mL (p < 0.05). Cytotoxic and anticancer activities were evaluated in MIA PaCa-2 pancreatic cancer cells and healthy human dermal fibroblasts. The extract exhibited selective cytotoxicity toward cancer cells (IC₅₀ = 0.16 mg/mL), with approximately fivefold lower toxicity in healthy cells. Cell cycle analysis demonstrated G0/G1 arrest, while the Annexin V assay revealed dose-dependent apoptosis (p < 0.0001). DNA damage analysis further supported its anticancer potential. Overall, HTE exhibits potent antioxidant, anti-inflammatory, and selective anticancer activities by reducing oxidative stress, inducing cell cycle arrest, and promoting apoptosis, highlighting its potential as a therapeutic agent.

Iron overload induces oxidative stress, lipid peroxidation, and inflammatory responses, collectively contributing to cellular and tissue injury. Although synthetic iron chelators are widely used in clinical practice, their associated adverse effects and treatment-related costs highlight the need to investigate naturally derived compounds as potential alternative therapeutic agents. This study comprehensively evaluated the iron-chelating, antioxidant, and anti-inflammatory properties of hazelnut samples encompassing Giresun-quality (Beşikdüzü, Vakfıkebir, and Çarşıbaşı), Levant-quality (Araklı, Arsin, and Yomra), and Pikola-type varieties, alongside extracts derived from defatted hazelnut pulp. Following qualitative and quantitative phytochemical characterization, antioxidant capacity was assessed using DPPH, CUPRAC, FRAP, and TOAC assays, while iron-binding capacity was evaluated under simulated gastric (pH 2) and intestinal (pH 6) conditions using atomic absorption spectroscopy and the ferrozine assay. To investigate hepatic protection, the iron-chelating potential of the extracts was examined in Hep3B cells exposed to iron overload. Extract C (80% ethanolic extract of ground hazelnuts) exhibited the most pronounced iron-chelating activity, achieving iron-binding efficiencies of 77–88% under simulated gastrointestinal conditions and 90% in the ferrozine assay, while decreasing intracellular iron accumulation in Hep3B cells by approximately 83–84%. Furthermore, Extract C effectively mitigated iron-induced oxidative stress, as evidenced by reduced malondialdehyde (MDA) levels and the restoration of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). In lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, the extracts additionally suppressed nitrite accumulation and decreased prostaglandin E₂ (PGE₂), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels. Our findings highlight the potential of hazelnut-based extracts as therapeutic candidates for the management of iron overload owing to their iron-chelating, antioxidant, and anti-inflammatory properties.