Bioactive chitosan-coated nano-Artemisia judaica extract-loaded bilosomes: Development, characterization, and biological potential

Artemisia judaica (Aj) has attracted attention for its promising biological activities, but its optimal use requires further exploration. This study aims to enhance the efficacy of Aj by encapsulating it in bioactive nanoformulations, specifically bilosomes (BLs). To improve the quality attributes of Aj-loaded BLs, various lipid and chitosan (CS) concentrations were evaluated. Accordingly, Aj-loaded BLs (Aj-BLs) and CS-BLs (Aj-CS-BLs) were constructed and characterized with respect to their quality parameters, including particle size, zeta potential, and entrapment efficiency (EE%). In vitro antioxidant, antibacterial, and anticancer potentials were also assessed. The bioactive contents of Aj were determined to be 147.5 mg of Gallic Acid equivalents and 53.4 mg of Quercetin equivalents per gram, representing the total phenolic and flavonoid contents. The Ai-BLs formulations exhibited nanometric particle sizes (76.5 ± 1.4–93.8 ± 1.9 nm) and a low PDI (< 0.3). They showed negative zeta potentials (-25.4 ± 1.5 to −37.4 ± 2.2 mV) with EE% ranging from 54.7 ± 3.0–81.9 ± 1.9 %, indicating good loading efficiency. Based on these results, Aj-CS-BLs-F3 was further coated with different concentrations of CS (0.1, 0.2, and 0.5 mg/mL), resulting in an increase in vesicle sizes (209.2 ± 2.3–284.1 ± 4.2 nm) and high PDI (< 0.4), positive zeta potential (29.1 ± 1.4–41.4 ± 1.3 nm), and EE% values (72.1 ± 3.3–44.5 ± 2.3 %). Among the formulations, Aj-CS-BLs-F3 and Aj-CS-BLs-F3–0.1 showed the best characteristics, with favorable in vitro release profiles, spherical appearance, and enhanced bioadhesion. Aj-CS-BLs-F3–0.1 demonstrated superior antioxidant, antibacterial (against S. aureus and E. coli), and anticancer activity (IC50 of 29.1 µg/against A549 lung cancer cells). Furthermore, the anti-inflammatory activity was examined; Aj-CS-BLs-F3–0.1 showed a significant reduction in pro-inflammatory cytokines (IL-6 and IL-1β) and an increase in IL-4 expression. Additionally, Aj-CS-BLs-F3–0.1 increased BAX, Caspase-3, and p53 gene expression and reduced Bcl-2 gene expression. In conclusion, these results highlight the potential of Aj-CS-BLs-F3–0.1 as an effective nanoformulation for oxidative stress-related diseases, infections, and cancer treatment. • Development of Aj-loaded bilosomes (Aj-BLs) and coated with chitosan (CS-BLs). • High drug entrapment and reduced particle size were achieved by these bilosomes. • The antioxidant and antibacterial activities of Aj were enhanced upon CS loading. • The cytotoxic activity of Aj-CS-BLs against A549 cells was improved.