Development, optimization, and evaluation of ketoconazole loaded transniosomal gel for enhanced dermal delivery for skin fungal infection

The present study aimed to develop and optimize ketoconazole (KTZ)-loaded transniosomes (TN) for improved dermal delivery and therapeutic efficacy. KTZ was characterized using differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) to confirm its thermal properties and chemical integrity. KTZ-loaded TN vesicles were formulated via the thin-film hydration method using Leciva-S70, cholesterol, Span 60, and sodium cholate. The formulation was optimized in terms of vesicle size, polydispersity index (PDI), and entrapment efficiency (%EE) using a three-factor, three-level Box-Behnken design. The optimized TN exhibited a vesicle size of 105.2 ± 2.15 nm, PDI of 0.29 ± 0.02, zeta potential of −29.63 ± 2.21 mV, and %EE of 87.63 ± 5.97. Transmission electron microscopy (TEM) confirmed spherical morphology. In vitro release studies demonstrated sustained drug release (94.97 ± 2.91% over 24 h) compared to KTZ suspension (43.49 ± 2.98%), following non-Fickian diffusion kinetics. Antioxidant activity, assessed via 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, showed enhanced free radical scavenging for TN compared to pure KTZ. The optimized TN was incorporated into a Carbopol 934 P gel matrix, exhibiting favorable pH (7.1 ± 0.1), spreadability, extrudability, and mechanical properties. Ex vivo permeation studies revealed significantly higher KTZ flux from TN gel (5.895 µg/cm2/h) versus conventional gel (3.560 µg/cm2/h). Dermatokinetic analysis indicated increased drug retention in epidermal and dermal layers with TN gel. Short-term stability studies demonstrated no changes in physicochemical properties over three months. Overall, the KTZ-loaded TN gel represents a promising nanocarrier system for enhanced topical delivery, improved skin penetration, and sustained therapeutic action.