Pharm Dev Technol. 2026 May 14:1-23. doi: 10.1080/10837450.2026.2673037. Online ahead of print.
ABSTRACT
Topical administration of non-steroidal anti-inflammatory drugs (NSAIDs) is often limited by poor skin permeability and a short duration of action. Solid lipid nanoparticles (SLNs) represent a promising carrier system capable of enhancing dermal drug delivery while sustaining local therapeutic effects. The present study aimed to formulate and optimize ketoprofen (KP)-loaded SLNs to enhance the drug’s therapeutic efficacy in topical inflammatory conditions. Modeling and optimization of formulation components were performed using a mixture design (MD) approach. SLNs were prepared using two methods: hot melting and solvent evaporation. The prepared formulations were characterized in terms of particle size, zeta potential, entrapment efficiency, and in vitro drug release profiles. Pharmacodynamic evaluation was conducted in rats using the carrageenan-induced paw edema model and compared with a marketed formulation (FASTUM® gel 2.5%).The optimized SLNs exhibited a particle size of 51.9 ± 4.55 nm, a polydispersity index (PDI) of 0.398 ± 0.02, and a zeta potential of -14.2 ± 0.61 mV, indicating acceptable colloidal stability. The optimized KP-SLN formulation produced a significant reduction in paw edema volume (57.65%) in pre-treated rats (P < 0.05), along with significant decreases in inflammatory mediators prostaglandin E2 (PGE2) and tumor necrosis factor-α (TNF-α) levels by 55.6% and 58.4%, respectively, compared with the carrageenan control group. Furthermore, the SLN-based gel demonstrated markedly higher bioadhesion (+81%) and a two-fold increase in permeation flux compared with the pure drug gel.Overall, the optimized ketoprofen SLN gel achieved enhanced bioadhesion, skin permeation, and anti-inflammatory efficacy, confirming the potential of lipid nanoparticle-based systems for topical NSAID delivery. This strategy provides a rational, statistically optimized platform for improving localized therapy while minimizing systemic adverse effects.
PMID:42133922 | DOI:10.1080/10837450.2026.2673037
