Cationic bakuchiol-loaded lipid nanoparticles enhance skin permeation and modulate neuro-immune inflammation and itch pathways in atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by recurrent pruritus and epidermal barrier dysfunction. The long-term use of topical corticosteroids is limited by local and systemic adverse effects, including skin atrophy. Here, we developed a cationic lipid nanoparticle (LNP) platform for the topical delivery of bakuchiol (BKC), a hydrophobic plant-derived bioactive with potent anti-inflammatory but limited aqueous solubility and skin permeation. The formulated BKC-LNPs showed high encapsulation efficiency and stable nanoscale physicochemical properties. By promoting interaction at the negatively charged skin interface, the cationic surface design improved cutaneous delivery compared with free BKC. In vitro, BKC-LNPs suppressed NF-κB activation and reduced the expression of pro-inflammatory mediators. The formulation also demonstrated significant anti-melanogenic efficacy, addressing post-inflammatory hyperpigmentation (PIH) - a debilitating chronic sequela of AD. In a murine model of AD-like skin inflammation, topical BKC-LNP treatment reduced ear swelling, epidermal hyperplasia, and inflammatory cell infiltration, and downregulated the pruritogenic mediators IL-31 and TSLP. In addition, BKC-LNPs upregulated barrier-related markers associated with epidermal homeostasis. Together, these findings identify cationic BKC-LNPs as a promising, multi-functional non-steroidal biomaterial platform for modulating inflammation, pruritus, pigmentation, and barrier recovery of AD.