*Article* **The Unique Carboxymethyl Fenugreek Gum Gel Loaded Itraconazole Self-Emulsifying Nanovesicles for Topical Onychomycosis Treatment**

**Ali Alqahtani <sup>1</sup> , Bhavana Raut <sup>2</sup> , Shagufta Khan 2,\*, Jamal Moideen Muthu Mohamed <sup>3</sup> , Adel Al Fatease <sup>4</sup> , Taha Alqahtani <sup>1</sup> , Ali Alamri <sup>4</sup> , Fazil Ahmad <sup>5</sup> and Venkatesan Krishnaraju <sup>1</sup>**


**Abstract:** The novel itraconazole (ITZ) nail penetration enhancing self-emulsifying nanovesicles (ITZnPEVs) loaded in carboxymethyl fenugreek gum (CMFG) gel circumvent the systemic onychomycosis treatment. The ITZ-nPEVs were prepared by the thin film hydration technique, and the particle size (PS), zeta potential (ZP), drug content (DC), entrapment efficiency (% EE), deformity index (DI), viscosity, morphology, and physical stability of the ITZ-nPEVs were measured. In terms of nail hydration, transungual drug absorption, and antifungal efficacy against *Candida albicans*, the chosen ITZ-nPEVs, nPEV-loaded CMFG (CMFG-ITZ-nPEVs) gel, and the commercialized Itrostred gel were compared. The ITZ-nPEVs showed spherical structure with high DC, % EE, low PS and PDI and positive ZP of ITZ ranging from 95.36 to 93.89 mg/5 mL and 95.36–96.94%, 196.55–252.5 nm, 0.092–0.49, and +11.1 to +22.5 mV, respectively. Compared to the Itrostred gel, the novel ITZ-nPEVs exhibited hydration enhancement factor for 24 h (HE24) of 1.53 and 1.39 drug uptake enhancement factor into nail clippings. Moreover, zone of inhibitions for ITZ-nPEVs (27.0 ± 0.25 mm) and CMFG-ITZ-nPEVs (33.2 ± 0.09 mm) against *Candida albicans* were significantly greater than that of Itrostred gel (22.9 ± 0.44 mm). For clinical investigation on onychomycotic patients, a nail penetration enhancer containing ITZ-nPEV-loaded CMFG gel presents a highly promising approach.

**Keywords:** itraconazole; onychomycosis; self-emulsifying nanovesicles; transungual; anti-fungal
