A Novel <i>Eurycoma Longifolia</i> ‐Loaded Flexible Nano‐Liposome Gel Formulation: Preparation, Characterization, In Vitro and In Vivo Studies

Abstract Sub‐health problems are becoming increasingly prevalent in contemporary society. Eurycoma longifolia is widely utilized to alleviate sub‐healthy conditions and other ailments owing to its ability to enhance physical constitution. However, its oral administration is compromised by the hepatic first‐pass effect, which significantly reduces bioavailability. Thus, developing efficient and safe transdermal formulations is essential to overcome this limitation. In this study, network pharmacology and molecular docking were first employed to identify eurycomanone as the model drug. Subsequently, a eurycomanone‐loaded flexible nanoliposome gel (EN‐FNLG) was developed and optimized. The formulation was characterized based on morphology, particle size, zeta potential, and infrared spectroscopy. Transmission electron microscopy revealed that the EN‐FNL particles were approximately spherical with a smooth surface. The encapsulation efficiency and drug loading capacity of EN‐FNL were determined to be 64.88% and 1.37%, respectively. In vitro skin permeation studies demonstrated that EN‐FNLG exhibited sustained‐release properties and caused no skin irritation. In vivo pharmacokinetic studies indicated that the AUC of EN‐FNLG was 4.14‐fold ( p &lt; 0.01) and 1.45‐fold ( p &lt; 0.05) higher than that of the solution group and conventional gel group, respectively. Similarly, the half‐life ( T 1/2 ) was 4.70‐fold ( p &lt; 0.01) and 1.17‐fold longer, respectively. These findings suggest that EN‐FNLG could represent a promising strategy for developing functionalized patches based on medicinal and food ingredients.