High payload dexamethasone palmitate-loaded solid lipid nanoparticles for enhanced anti-inflammatory effects in acute skin inflammation model

Purpose: Dexamethasone palmitate (DXPL) is a lipophilic derivative of dexamethasone (DXM) used to overcome the low drug-loading capacity and immediate release characteristics of DXM from nanoparticles. In this study, we investigated the potential of DXPL-loaded solid lipid nanoparticles (DXPL-SLNs) to increase drug encapsulation efficiency, prolong drug release, and alleviate skin inflammation. Methods: DXPL-SLNs were prepared using the nano-emulsion template technique with trilaurin as a lipid matrix and Tween 20, Span 20, and Brij 58 as a surfactant mixture. The physicochemical properties of DXPL-SLNs were examined in terms of particle size, polydispersity index, zeta potential, encapsulation efficiency, loading capacity, morphology, and crystalline behavior. The in vitro release profile of DXM from the DXPL-SLNs incubated in mouse plasma was assessed using a plasma conversion assay. In vivo anti-inflammatory effects of topically applied DXPL-SLNs were evaluated in mice with 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced ear edema. Results: The optimized DXPL-SLNs (DXPL/trilaurin/Tween 20/Span 20/Brij 58:4/2/2/0.2/4, w/w ratio, respectively) displayed a mean particle size of 182.8 ± 2.7 nm with a very high drug loading capacity of 30.4%. DXPL-SLNs showed substantially prolonged drug release in mouse plasma compared to DXPL solution. Furthermore, DXPL-SLNs showed enhanced anti-inflammatory effects by efficiently reducing TPA-induced ear edema. Conclusion: These findings suggest that DXPL-SLNs have great potential as anti-inflammatory therapeutics against acute skin inflammation.