Flavonoids play an important role in preventive and therapeutic research due to their significant antioxidant properties. However, their application is limited by several pharmacokinetic drawbacks, such as poor water solubility and low bioavailability. Cyclodextrin-based delivery systems offer an opportunity to overcome these disadvantages. Cyclodextrins are able to form stable, water-soluble inclusion complexes with flavonoids, thereby improving their solubility, chemical stability, and antioxidant activity. This review summarizes the structural characteristics and complexation mechanisms of various flavonoid–cyclodextrin complexes and examines how these interactions influence biological activity. Special attention is given to nanotechnological formulations—such as liposomes, nanofibers, and nanosponges—that enable targeted drug delivery and enhanced therapeutic efficacy. The aim of this review is to provide a comprehensive overview of the role of cyclodextrin-based carriers in the formulation of flavonoids and to highlight the future potential of these systems in modern therapeutics and functional product development.

Tapinarof is a novel aryl hydrocarbon receptor (AhR) agonist that has recently been approved for the treatment of psoriasis. Although its clinical efficacy has been proven, in psoriasis, hyperkeratotic plaques and damaged barrier hinder drug penetration from conventional creams and ointments, resulting in poor bioavailability in the deeper layers of the skin. Innovative drug delivery systems can improve targeted action and reduce potential side effects. The primary goal of this study was to evaluate whether tapinarof-loaded nanogels enhance the anti-inflammatory, anti-proliferative, and anti-migratory effects of tapinarof at the cellular level using an in vitro HaCaT-THP-1 co-culture model. Initially, experiments were performed using real-time cell analysis (RTCA), and a concentration of 10 µM was found to be the most effective, showing significant cell proliferation inhibition compared to imiquimod and free tapinarof. To demonstrate cell proliferation and migration during inflammatory conditions, a wound healing assay was performed, which showed inhibited cell migration. Subsequently, the levels of inflammatory cytokines (TNF-α, IFN-γ, IL-17A, IL-23) were analyzed by ELISA, which demonstrated that tapinarof incorporated into nanogels reduced cytokine production more effectively than the drug alone. Quantitative PCR (qPCR) analysis confirmed Imiquimod (IMQ)-induced upregulation of Tnf-α and Ifn-γ, whereas Il-17a and Il-23 did not show measurable transcriptional changes under the experimental conditions. Finally, inhibition of p65 subunit nuclear translocation were observed during NF-κB pathway activation in THP-1 cells by immunofluorescence staining. Overall, our results indicate that nanogel-based delivery systems exhibit enhanced biological effects of tapinarof compared to the free drug in an in vitro psoriasis-like co-culture model, highlighting their potential as therapeutic tools for the treatment of various inflammatory skin diseases.

Background: Artemisia annua 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 Artemisia annua extract, supplemented with hyaluronic acid and dexpanthenol, and to evaluate their physicochemical characteristics as well as their biological activities in vitro and in vivo. Methods: Select bioactive constituents of the Artemisia annua 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. Results: The extract contained high levels of methylated flavonoids and sesquiterpenes characteristic of Artemisia annua. 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, Artemisia annua hydrogels accelerated wound healing by two to three days compared with untreated wounds. Conclusions: These results confirm the promise of Artemisia annua hydrogels for topical wound care and highlight the beneficial contributions of hyaluronic acid and dexpanthenol to their structural and therapeutic performance.