20-Hydroxyecdysone-Loaded Niosomes as a Novel Nano-Therapeutic Platform for Psoriasis: In Vitro Characterization and...

Background/Objectives: Psoriasis is an incurable chronic immune-mediated inflammatory skin disorder for which effective topical treatment remains essential. Given the reported anti-inflammatory and dermatological potential of 20-hydroxyecdysone (20HE), this study evaluated its biological activity in normal and psoriatic keratinocytes and developed stable 20HE-loaded niosomes intended for potential future dermal delivery. Methods: The biological activity of 20HE was assessed in human epidermal keratinocytes (HEKs) and psoriasis-patient-derived keratinocytes (PHEKs) after 48 h of treatment by quantifying selected cytokines. Niosomes were prepared by thin-film hydration, rehydrated with water or citrate buffer, and sonicated. The formulations were characterized for particle size, polydispersity index, zeta potential, pH, encapsulation efficiency (EE), and 21-day storage stability. Potential in vivo toxicity was assessed in Danio rerio embryos by monitoring mortality, sublethal developmental changes, and locomotor behavior after exposure to nanoformulations for up to 96 h post-fertilization. Results: 20HE showed selective anti-inflammatory activity in PHEK cells, reducing IL-4, IL-17A, and IL-22 levels by 20-34% under elevated inflammatory conditions, without affecting healthy HEK cells. The formulations had particle sizes below 300 nm and acceptable polydispersity and zeta potential values, and they remained stable during storage. In the Danio rerio embryo model, the 1A/water caused sublethal developmental abnormalities at 96 hpf, whereas 1C/water (with 20HE) was associated only with mild pericardial edema after prolonged exposure. No significant behavioral alterations were observed across the tested concentration range, and the Lowest Observed Effect Concentration for 20HE was 20 μM. Conclusions: Free 20HE reduced the levels of IL-4, IL-17A, and IL-22 in PHEK cells, indicating its modulatory effect on cytokine production under the investigated inflammatory conditions. The developed 20HE-loaded niosomes showed favorable physicochemical properties and short-term stability, supporting their potential as candidate nanocarrier systems for future dermal application studies. The findings of the present study provide a basis for further investigation, particularly studies on drug release from the niosomal formulation and skin permeation from the final pharmaceutical dosage form.