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Apigenin (APG), a natural bioactive flavonoid, has multiple pharmacological effects. However, its poor aqueous solubility hinders its clinical benefits. The work aimed to develop novel apigenin-loaded niosomes (APG-NIO) with ecological probe sonication techniques. The formulation was statistically optimized by Box-Behnken design (BBD), and the independent variables were selected as Span 80 (X1), Poloxamer 188 (X2), and Tween 80 (X3) at three levels, and the dependent variables were identified as particle size (Y1), polydispersity index (Y2)