Anti-Inflammatory Effects of Curcumin-Based Nanoparticles Containing α-Linolenic Acid in a Model of Psoriasis In...

Background/Objectives. Psoriasis is a common chronic skin inflammatory disorder pathogenetically associated with genetic, environmental, and immunological factors. The hallmarks of psoriatic lesions include sustained inflammation related to alterations in the innate and adaptive immune response, uncontrolled keratinocyte proliferation, differentiation, and death, as well as dysregulated crosstalk between immune cells and keratinocytes. In search of novel therapeutic strategies based on the use of natural products and dietary components to combine to the available conventional and innovative therapeutics, we explored the anti-inflammatory, antioxidant, and immunomodulatory activities of Curcumin (CU)-based solid lipid nanoparticles (SLNs) carrying the omega-3 fatty acid linolenic acid (LNA) in an in vitro model of psoriasis that had been previously constructed and characterized by us. Methods. This in vitro model consists of differentiated in vitro THP-1 macrophages (Mφs) and NCTC-2544 keratinocytes exposed or not to conditioned medium (CM) from Mφs treated with the Toll-like receptor-7 ligand imiquimod (IMQ). Results. In Mφs, the treatment with CU-LNA-SLNs inhibited the IMQ-induced expression of proinflammatory cytokines (IL-23, IL-8, IL-6: 43%, 26.5% and 73.7% inhibition, respectively, vs IMQ-treated Mφs), as well as the hyperproliferative response (12.8% inhibition vs IMQ-treated Mφs) and the increase in cell death observed in keratinocytes treated with Mφ-derived CM (64.7% inhibition). Moreover, in the same conditions, CU-LNA-SLNs reverted to control levels of the increased keratinocyte expression of two markers of ferroptosis, a form of death recently involved in the pathogenesis of psoriasis (TFRC and MDA: 13.4% and 56.1% inhibition, respectively). Conclusions. These results suggest that CU-LNA-SLNs could inhibit psoriatic inflammation, as well as the hyperproliferation and death of keratinocytes in psoriatic lesions, and could be considered as a new possible therapeutic strategy for psoriasis to be further evaluated for the topic treatment of psoriatic skin in vivo.