Statistically Optimized Tacrolimus and Thymoquinone Co-Loaded Nanostructured Lipid Carriers Gel for Improved Topical Treatment of Psoriasis

The aim of this investigation was to develop and analyze a tacrolimus and thymoquinone co-loaded nanostructured lipid carriers (TAC-THQ-NLCs)-based nanogel as a new combinatorial approach for the treatment of psoriasis. The NLCs were formulated by an emulsification-solvent-evaporation technique using glyceryl monostearate, Capryol 90 (oil), and a mixture of Tween 80 and Span 20 as a solid lipid, liquid lipid, and surfactant, respectively. Their combination was optimized using a three-factor and three-level Box–Behnken design (3(3)-BBD). The optimized TAC-THQ-NLCs were observed to be smooth and spherical with a particle size of 144.95 ± 2.80 nm, a polydispersity index of 0.160 ± 0.021, a zeta potential of −29.47 ± 1.9 mV, and an entrapment efficiency of >70% for both drugs. DSC and PXRD studies demonstrated the amorphous state of TAC and THQ in the lipid matrix of the NLCs. An FTIR analysis demonstrated the excellent compatibility of the drugs with the excipients without interactions. The TAC-THQ-NLC-based nanogel (abbreviated as TAC-THQ-NG) exhibited a good texture profile and good spreadability. The in vitro release study demonstrated a sustained drug release for 24 h from the TAC-THQ-NG that followed the Korsmeyer–Peppas kinetic model with a Fickian diffusion mechanism. Moreover, the TAC-THQ-NG revealed significantly higher dose-dependent toxicity against an HaCaT cell line compared to a TAC-THQ suspension gel (abbreviated as TAC-THQ-SG). Furthermore, the developed formulations demonstrated antioxidant activity comparable to free THQ. Confocal microscopy revealed improved permeation depth of the dye-loaded nanogel in the skin compared to the suspension gel. Based on these findings, it was concluded that TAC-THQ-NG is a promising combinatorial treatment approach for psoriasis.