<p><b>Background</b>: The present work focuses on the development of ultra-small solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) encapsulating cyclosporine and calcipotriol, further incorporated into gel, increasing their penetration through the skin.</p> <p><b>Research design and methods</b>: Developed SLN and NLC were characterized regarding particle size, zeta potential, %entrapment efficiency and dispersed into carbopol 934P-NF gel. Gel was further characterized for rheological behavior and spreadability. <i>Ex vivo</i> dermatokinetic by tape stripping method, <i>in vitro</i> efficacy on HaCaT cell lines and <i>in vivo</i> efficacy on imiquimod induced psoriatic model in mice were evaluated.</p> <p><b>Results</b>: Ultra-small (size<100 nm) particles were formed with high entrapment efficiency and spherical morphology. <i>Ex vivo</i> dermatokinetic studies revealed deeper and confined drug penetration of lipid formulation gel in epidermal layers as compared to free drug. <i>In vitro</i> study on HaCaT cell lines depicted higher uptake and high efficacy owing to decrease in cell viability for NLC. The anti-psoriatic efficacy in BALB/c mice (evaluated on basis of cytokine levels and skin morphology) highlighted potential of drug-loaded NLC significantly higher as compared to drug loaded SLN and marketed formulation Betagel.</p> <p><b>Conclusions</b>: The study demonstrated that NLC gel had higher efficacy in psoriatic management and hold promise for further exploration.</p
