Mixture design-modelling and optimization of ketoprofen solid lipid nanoparticles for augmented anti-inflammatory activity following pharmacodynamic evaluation in rats

Abstract

Topical administration of non-steroidal anti-inflammatory drugs (NSAIDs) is often limited by poor skin permeability and short duration of action. Solid lipid nanoparticles (SLNs) offer a promising carrier system to enhance dermal delivery and sustain local therapeutic effects. This study aimed to formulate and optimize ketoprofen (KP)-loaded SLNs to improve its efficacy in topical inflammatory conditions. A mixture design was applied for modeling and optimization of formulation variables. SLNs were prepared using hot melting and solvent evaporation techniques and characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, and drug release. Pharmacodynamic evaluation was conducted using a carrageenan-induced paw edema model in rats, compared with a marketed formulation (FASTUM gel 2.5%). The optimized SLNs showed a particle size of 51.9±4.55 nm, PDI of 0.398±0.02, and zeta potential of -14.2±0.61 mV, indicating acceptable stability. The optimized formulation significantly reduced paw edema by 57.65% and decreased PGE2 and TNF-α levels by 55.6% and 58.4%, respectively (P < 0.05). Additionally, the SLN gel exhibited enhanced bioadhesion (+81%) and doubled permeation flux compared to the pure drug gel. These findings support SLNs as an effective platform for topical NSAID delivery.