A “controlled assembly” strategy for constructing Coptidis Rhizoma self-assembled nanoparticles to ameliorate inflammatory damage in Atopic dermatitis

Atopic dermatitis (AD) is a prevalent chronic inflammatory disorder requiring effective therapeutic intervention. Self-assembled nanoparticles derived from traditional Chinese medicine (TCM) decoctions have gained increasing attention for their potential clinical applications in AD treatment. However, the self-assembly process of TCM occurs simultaneously with the extraction of active ingredients, leading to poor stability and uniformity of the self-assembled nanoparticles, which results in unpredictable therapeutic efficacy. In this study, we propose an innovative "controlled assembly" strategy to improve the self-assembly process of decoction. <i>Coptidis Rhizoma</i> self-assembled nanoparticles (CR-SAN) were constructed via hydrochloric acid-assisted aqueous extraction followed by pH-driven assembly. CR-SAN exhibited a spherical morphology with an average particle size of 234.9 ± 5.1 nm and a polydispersity index of 0.21 ± 0.03. <i>In vitro</i> permeation studies demonstrated that CR-SAN enhances skin permeation and retention by disrupting the stratum corneum structure, altering lipid organization, and modifying the secondary structure of keratin. Notably, CR-SAN demonstrated remarkable anti-inflammatory efficacy in both <i>in vitro</i> and <i>in vivo</i>. NLRP3, the most distinctive member of the NOD-like receptors (NLRs) family, plays a pivotal role in inflammatory regulation. Integrative network pharmacology and transcriptomic analysis revealed that CR-SAN significantly downregulated the expression of NLRP3 pathway (including GSDMD and IL-33) in AD models, thereby alleviating the itch-scratch cycle and preserving skin barrier function. Collectively, the development of CR-SAN establishes a novel therapeutic strategy for AD management through NLRP3 pathway modulation, while also providing new insights into the advancement of self-assembled nanoparticles derived from TCM.