Self-assembled hyaluronic acid nanoparticles (HA-NPs) are widely used as drug delivery systems because HA has biocompatible, non-toxic, and non-immunogenic. Recently, drug-free HA-NPs have been shown to exert therapeutic effects in type 2 diabetes and atherosclerosis. Here, I investigate the in vitro and in vivo therapeutic efficacy of an empty HA-NP itself in psoriasis, the most common chronic inflammatory skin disease, after topical treatment via transcutaneous delivery. HA-lithocholic acid (LCA) NPs are amphiphilic compounds composed of hydrophilic HA and hydrophobic LCA that self-assemble in an aqueous environment to form sphere-shaped NPs. HA-LCA NPs inhibited the lipopolysaccharide (LPS)-induced polarization of the human monocyte cell line THP-1 into pro-inflammatory M1 macrophages and reduced the expression of interleukin (IL)-23, a key player in psoriasis and inflammatory cascades. In addition, HA-LCA NPs decreased the expression of pro-inflammatory genes in the human keratinocyte cell line HaCaT stimulated with IL-17 and IL-22. Furthermore, transcutaneous administration of HA-LCA NPs resulted in significant localization into the dermis and epidermis in control and imiquimod (IMQ)-induced psoriasis mouse models, thereby effectively ameliorating psoriasis-like skin inflammation as reflected by reduced skin tissue thickening, inflammation, and cytokine expression. These results suggest that skin-penetrating HA-LCA NPs may serve as novel therapeutic agents for the treatment of human psoriasis-like dermatitis by suppressing the inflammatory response.
