Licofelone-Loaded Poly(d,l-Lactide-Co-Glycolide) Nanoparticles to Enhance Therapeutic Action: A Novel Approach for the Topical Management of Irritant Contact Dermatitis

Irritant contact dermatitis (ICD) is a common and potentially debilitating chronic skin disorder that affects a large proportion of the worldwide population. In the present work, licofelone (LF) was incorporated into poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles to design a topical nanocarrier systems intended to boost its therapeutic impacts in treatment of ICD. To achieve this objective, LF-loaded PLGA nanoparticles (PLGANPs) were fabricated utilizing the nanoprecipitation technique, and the formulation parameters were statistically optimized utilizing a D-optimal experimental design. Three independent variables were investigated: PLGA amount (X₁), poloxamer amount (X₂), and poloxamer type (X₃). The encapsulation efficiency (Y₁: EE%), particle size (Y₂: PS), polydispersity index (Y₃: PDI), and zeta potential (Y₄: ZP) were selected as dependent responses. The optimized formulation (P19) exhibited spherical morphology, with a particle size of 160.45 ± 0.42 nm, an encapsulation efficiency of 93.34 ± 0.26%, a PDI of 0.24 ± 0.009, and a zeta potential of -34.8 ± 0.27 mV. When incorporated into a gel, P19 displayed a sustained drug release profile and achieved 2.72-fold higher permeation across rat skin compared to a conventional LF gel. In vivo, topical application of P19 gel effectively alleviated xylene-induced ear dermatitis in mice. It markedly suppressed the inflammatory response and consequently decreased the immune expression of proinflammatory cytokines. The histopathology further confirmed a pronounced reduction in dermal edema and inflammatory cell infiltration, corroborating the biochemical findings. Collectively, these results indicate the potential of LF-loaded PLGA nanoparticles as a novel topical therapeutic system for ICD.