<![CDATA[Usnic acid, a secondary metabolite derived from Usnea sp., exhibits diverse pharmacological activities; however, its therapeutic utility is constrained by poor aqueous solubility and risk of hepatotoxicity upon oral administration. To overcome these limitations, this study aimed to develop a self-nanoemulsifying drug delivery system (SNEDDS) of usnic acid tailored for topical application. The formulation was optimized via a pseudoternary phase diagram and characterized using a particle size analyzer (PSA) and transmission electron microscopy (TEM). The optimized SNEDDS—comprising grapeseed oil, Cremophor RH 40, and polyethylene glycol 400—exhibited rapid emulsification (0.87 ± 0.05 s) and high transmittance (99.12 ± 0.34%). PSA analysis revealed a globule size of 132.45 ± 4.21 nm, a polydispersity index (PDI) of 0.32 ± 0.02, and a zeta potential of −34.76 ± 1.15 mV, aligning with TEM observations that confirmed a spherical morphology. This optimized system was subsequently incorporated into a Carbopol Ultrez 30 hydrogel, yielding a homogeneous formulation with a pH of 5.86 ± 0.12 and a spreadability of 5.74 ± 0.28 cm. Upon incorporation into the gel framework, the SNEDDS maintained favorable characteristics, exhibiting a globule size of 148.67 ± 5.02 nm nm, a PDI of 0.36 ± 0.03, and a zeta potential of 31.42 ± 1.27 mV. Finally, in vitro release studies demonstrated that the SNEDDS hydrogel achieved an approximate two-fold increase in usnic acid release over 24 h compared to a conventional hydrogel, highlighting its potential as an effective topical delivery system]]>
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