Delivery of penetration-enhancing antioxidant polyphenol nanoparticles with Codonopsis pilosula polysaccharide microneedles for synergistic treatment of psoriasis

Poor drug penetration due to local skin thickening and microenvironmental redox imbalance remain a critical challenge in the treatment of epidermal diseases. Considering that oxidative stress due to the overproduction of Reactive Oxygen Species (ROS) in the skin microenvironment is one of the main mechanisms in the pathogenesis of psoriasis, we developed a ROS-sensitive transdermal drug delivery system to enhance topical treatment of psoriasis. Cross-linked cyclodextrin metal-organic framework (COF) containing curcumin (CUR) was dispersed in two types of dissolving polysaccharide microneedles (CPPAP-MNs-CUR@COF, CPPNP-MNs-CUR@COF) made from Codonopsis pilosula neutral polysaccharides (CPPNP) and acidic polysaccharides (CPPAP) for topical administration. COF contains peroxyoxalate bonds that scavenge H₂O₂, hydrolyse and eliminate ROS generated at the site of inflammation. Microneedles (MNs) that break through the skin's physical barrier improve drug penetration, while Codonopsis pilosula Polysaccharides (CPP) can synergise with CUR to significantly attenuate inflammation and oxidative stress and ameliorate imiquimod (IMQ)-induced symptoms of psoriasis in mice through inhibition of the IL-23/IL-17 inflammatory axis. It is a promising drug delivery system that is expected to provide new strategies for the topical treatment of psoriasis in the clinical setting.