This work aimed to elaborate an optimised fluticasone propionate (FP)-loaded solid lipid nanoparticles (SLNs) to enhance FP effectiveness for topical inflammatory remediation. The influences of drug amount, lipid, and surfactant ratios, on drug release pattern and stability were investigated utilising Box-Behnken design. Elaboration, characterisation, and pharmacodynamic evaluation in comparison with the marketed formulation (Cutivate (R) cream, 0.05%w/w FP), were conducted for the optimised SLNs. The optimised SLNs with a size of 248.3 +/- 1.89 nm (PDI = 0.275) and -32.4 +/- 2.85 mV zeta potential were evidenced good stability physiognomies. The optimised SLNs pre-treated rats exhibited non-significant difference in paw volume from that of the control group and showed a significant reduction in both PGE(2) and TNF-alpha levels by 51.5 and 61%, respectively, in comparison with the Carrageenan group. The optimised FP-loaded SLNs maximised the efficacy of FP towards inflammation alleviation that increase its potential as efficient implement in inflammatory skin diseases remediation.