Preparation and Investigation of Artemisia annua L.-Loaded Alginate Hydrogels with Excipients

<b>Background:</b><i>Artemisia annua</i> L. is a medicinal plant with documented antimicrobial, antioxidant, and anti-inflammatory properties. Although widely studied for internal therapeutic applications, its topical use-especially in hydrogel-based systems-has not been thoroughly investigated. The aim of this study was to develop sodium alginate hydrogels containing <i>Artemisia annua</i> extract, supplemented with hyaluronic acid and dexpanthenol, and to evaluate their physicochemical characteristics as well as their biological activities in vitro and in vivo. <b>Methods:</b> Select bioactive constituents of the <i>Artemisia annua</i> extract were quantified using liquid chromatography coupled with electrospray ionization mass spectrometry (LC-ESI-MS). Hydrogels were prepared by cross-linking sodium alginate with a calcium carbonate-glucono-delta-lactone system and were formulated with or without hyaluronic acid and dexpanthenol. Physicochemical evaluations included measurements of moisture content, water-retention capacity, gelation time, and pH. The hydrogel microstructure was examined by scanning electron microscopy (SEM). Antioxidant activity was assessed using three methods: the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, the ferric reducing antioxidant power (FRAP) assay, and the cupric reducing antioxidant capacity (CUPRAC) assay. Biocompatibility and regenerative effects were analyzed using cell viability assays and an in vitro scratch wound model on human keratinocyte cells. In vivo wound-healing efficacy was examined in rats with full-thickness skin excisions. <b>Results:</b> The extract contained high levels of methylated flavonoids and sesquiterpenes characteristic of <i>Artemisia annua</i>. Hydrogels supplemented with hyaluronic acid and dexpanthenol exhibited improved hydration stability and higher porosity. All formulations demonstrated measurable antioxidant activity, and those containing hyaluronic acid showed the strongest effects. The preparations were biocompatible and enhanced keratinocyte migration in vitro, with the combined hyaluronic acid-dexpanthenol formulation promoting the fastest wound closure. In vivo, <i>Artemisia annua</i> hydrogels accelerated wound healing by two to three days compared with untreated wounds. <b>Conclusions</b>: These results confirm the promise of <i>Artemisia annua</i> hydrogels for topical wound care and highlight the beneficial contributions of hyaluronic acid and dexpanthenol to their structural and therapeutic performance.