Does the technical methodology influence the quality attributes and the potential of skin permeation of Luliconazole loaded transethosomes?

Abstract

Luliconazole (LCZ) is a novel topical imidazole medication with broad-spectrum antifungal activity. Unfortunately, the high potential of LCZ for topical antifungal activity is hampered by its low solubility and low skin permeability that required long-term therapy with frequent administration for a full recovery. So, this study aimed to enhance the skin permeation of LCZ through its loading in ultradeformable nanovesicles, transethosomes (TE), using either ethanol injection sonication or thin-film hydration methods. The prepared nanovesicles were characterized for vesicles size, zeta potential, entrapment efficiency, and in vitro drug release. Moreover, the ex vivo skin permeation and deposition via rat skin were estimated. In vitro characterization of the LCZ-TE displayed that the average vesicles size prepared by the ethanol injection method was 246.3 ± 0.56 versus 62.75 ± 0.16 nm with a thin-film method. Also, the zeta potential and encapsulation efficiency were 36.3 ± 0.81 mV and 82.35 ± 3.68% versus 49.4 ± 0.67 mV and 93.85 ± 1.78% in the ethanol injection sonication and thin-film hydration, respectively. Furthermore, the deposited percentage of LCZ in the skin by TE formulation prepared by thin film hydration (54.79 ± 5.23%) is more than 2-fold the percentage of LCZ solution in propylene glycol (PG) (25.26 ± 2.84%) and 1.5 fold more than TE prepared by ethanol injection (35.65 ± 4.354) due to the enhanced skin permeation and deposition of LCZ-TE. These results revealed the superiority of the thin film hydration technique in the enhancement of the quality attributes of the prepared nanovesicles and pointed out their potential in the treatment of fungal infections of the skin.