Formulation and Evaluation of a Luliconazole-Loaded Nanostructured Lipid Carrier Gel for Enhanced Topical Treatment of Fungal Infections

Objective: The present study aimed to formulate and systematically evaluate a luliconazole-loaded nanostructured lipid carrier (NLC) gel to enhance topical delivery, skin retention, and antifungal efficacy while minimizing systemic absorption and dosing frequency. Methods: Luliconazole-loaded nanostructured lipid carriers (NLCs) were prepared using the hot high-pressure homogenization method. Glyceryl monostearate was used as the solid lipid, while oleic acid was used as the liquid lipid, stabilized with Tween 80 and PEG 400. A central composite design within the Quality by Design framework was implemented to systematically optimize formulation variables. The optimized NLCs were tested for particle size, polydispersity index, zeta potential, drug entrapment efficiency, drug loading, particle shape, and compatibility between the drug and other ingredients. These properties were studied using techniques such as dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The optimized NLCs were then mixed with Carbopol 934 gel to prepare the final formulation. The prepared gel was evaluated for pH, viscosity, spreadability, uniformity of drug content, drug release, and drug release pattern. Skin permeation and drug retention were studied using pig ear skin. The stability of the gel was also tested under accelerated conditions for six months. Results: The optimized NLCs exhibited a mean particle size of 151.6 ± 5.8 nm with a narrow size distribution (PDI = 0.182 ± 0.015), zeta potential of -28.4 ± 3.6 mV, entrapment efficiency of 91.3 ± 2.8%, and drug loading of 4.86 ± 0.32%. TEM images revealed spherical, uniformly sized nanoparticles devoid of drug crystals. FTIR confirmed drug-excipient compatibility, while DSC and XRD demonstrated molecular dispersion and amorphization of luliconazole within the lipid matrix. The NLC gel showed optimal pH (6.12 ± 0.15), viscosity (4280 ± 320 cps), spreadability (4.86 ± 0.42 g·cm/s), and drug content (98.7 ± 1.4%). The in vitro drug release study showed that the drug was released quickly at first, followed by a slow and continuous release over 24 hours (92.6 ± 4.2%). The drug release followed the Higuchi model (R² = 0.9874), indicating that the drug was mainly released through diffusion. The ex vivo skin permeation study showed that the NLC gel allowed 3.8 times more drug to pass through the skin (126.4 ± 8.7 μg/cm²) and 4.2 times more drug to remain in the skin (18.6 ± 1.2 μg/g) compared to the conventional gel. The NLC gel maintained therapeutic concentrations above the minimum inhibitory concentration for 24 hours, with significantly reduced systemic absorption (3.2 ± 0.4 μg/mL vs. 8.7 ± 0.9 μg/mL). Accelerated stability studies confirmed excellent physical and chemical stability over 6 months. Conclusion: The luliconazole-loaded NLC gel represents a promising nanocarrier-based topical formulation that overcomes the pharmacokinetic limitations of conventional therapies, offering enhanced skin permeation, superior epidermal retention, sustained drug release, and reduced systemic absorption. This innovative formulation has the potential to enable once-daily dosing, improve patient compliance, and provide effective, safe treatment for superficial fungal infections with minimized side effects, warranting further clinical translation and industrial scale-up.

Hali tarjima qilinmagan