Voriconazole-loaded nanostructured lipid carriers (NLC) for drug delivery in deeper regions of the nail plate

Voriconazole-loaded nanostructured lipid carriers (VOR-NLC) were developed and drug penetration evaluated in porcine hooves in vitro. Synergistic effect of urea (Ur), selected among other known chemical enhancers according to hoof hydration potential, was also evaluated. VOR-NLC presented a high encapsulation efficiency (74.52±2.13%), approximate mean diameter of 230nm and were positively charged (+27.32±2.74mV). Stability studies indicated they were stable under refrigeration (4±2°C) for up to 150days. SEM images revealed hooves treated with VOR-NLC and VOR-NLC-Ur suffered a disturbance on the surface depicting high roughness and porosity. Permeation data showed a substantial VOR amount retained in superficial hooves sections independent of the formulation used (2.42±0.26; 2.52±0.36 and 2.41±0.60μg/cm² for unloaded VOR, VOR-NLC and VOR-NLC-Ur, respectively, p>0.05). Still, successive extractions, revealed the amount of VOR retained in deeper regions was significantly higher when VOR-NLC or VOR-NLC-Ur was used (0.17±0.04, 0.47±0.14 and 0.36±0.07μg/cm² for unloaded VOR, VOR-NLC and VOR-NLC-Ur, respectively, p<0.05). Such results indicate NLC are promising formulations for the management of onychomycosis. Further studies in diseased nail plates are necessary.