Arthritis is a chronic inflammatory disorder that impairs joint function and necessitates efficient localised treatment. This research aimed to formulate and optimise leflunomide-loaded nanostructured lipid carriers (NLCs) for topical delivery via a systematic Quality by Design technique. Dynasan 114 and corn oil were used as the solid and liquid lipids, respectively, and NLCs were formulated using high-speed homogenisation followed by probe sonication to achieve uniform particle size and stability. A dual experimental design approach was employed, using Plackett-Burman screening to identify critical formulation parameters, followed by Box-Behnken for formulation optimisation. This strategy resulted in optimised NLCs with a particle size of 125.5nm, a PDI of 0.188, a zeta potential of -15.5mV, and an entrapment efficiency of 92.20 ± 1.28%.% FT-IR, DSC, P-XRD, and TEM validated the amorphous dispersion of leflunomide within the lipid matrix and the spherical morphology of the NLCs. The optimised NLCs were integrated into a Carbopol 980 NF (0.75%) gel base, demonstrating appropriate rheological properties such as extrudability (176 g), adhesiveness (-112 g), and pH (6.92). The gel formulation demonstrated prolonged drug release (96% over 24 hours) and increased ex-vivo permeation with flux of 0.3632mg/cm2/hour, hence validating enhanced diffusion through the skin barrier. The in-vivo pharmacodynamic study using a carrageenan-induced paw edema model exhibited an 89.40% reduction in inflammation, exceeding the efficacy of the marketed leflunomide formulation. These findings suggest that the leflunomide-loaded NLC-based gel offers a promising platform for dermal drug distribution and enhanced anti-inflammatory activity.
Mewada et al. (Wed,) studied this question.