Objective: Ketoconazole is used in the treatment of superficial and systemic fungal infections.
It acts by blocking the synthesis of ergosterol, an essential component of the fungal cell membrane.
The purpose of this work was to formulate ketoconazole loaded nanostructured lipid carriers
formulation for skin targeting to minimize the adverse side effects and to prolong release.
Methods: The ketoconazole loaded nanostructured lipid carriers were optimized using 32 factorial design
to evaluate the effects of process and formulation variables. The nanostructured lipid carriers were
prepared by melt-dispersion ultra-sonication method. The formulations were finally incorporated into
polymeric gels of Carbopol 940 for convenient application. The gels were evaluated comparatively
with commercially available formulations of ketoconazole with respect to ex vivo skin permeation and
deposition study on human cadaver skin.
Results: Nanostructured lipid carriers showed average particle size, zeta potential, and percentage entrapment
in the range of 125.8 ± 1.8 to 295.0 ± 3.8 nm, -13.2 ± 1.1 to -30.9 ± 2.2 mV, and 69.47 ± 2.8
to 95.49 ± 4.5, respectively. Thermal studies revealed no drug-excipient incompatibility and amorphization
of ketoconazole. Ex vivo study of the gel exhibited prolonged drug release up to 12 h. In vitro
drug deposition study showed that the gel formulation can avoid the systemic uptake, better accumulative
uptake of the drug, and nonirritant to the skin compared to marketed formulation. Optimized formulation
exhibited better antifungal activity when compared to ketoconazole loaded gel and marketed
cream (Keto ® cream). Histolopathology results indicated no toxic effect on the skin.
Conclusions: These results indicate that developed nanostructured lipid-carriers gel formulation represents
a promising carrier for topical delivery of ketoconazole, having controlled drug release, and potential
of skin targeting.