Platycodon grandiflorus-loaded solid dispersion via hot-melt extrusion: A novel delivery system for mitigating allergic skin inflammation

초록

Skin dermatitis is sustained by dysregulated immune activation and barrier dysfunction, underscoring the need for practical, multi-target interventions with improved efficacy profiles. Guided by network pharmacology, we tested whether hot-melt extrusion (HME), a continuous solvent-free processing approach, can potentiate the antidermatitic activity of Platycodon grandiflorus (PG). We prepared an HME-processed PG formulation (PGH) and compared it with conventionally prepared PG across DNCB-induced dermatitis in NC/Nga mice, TNF-alpha/IFN gamma-stimulated HaCaT keratinocytes, and LPS-stimulated RAW264.7 macrophages. In vivo, PGH more effectively mitigated dermatitis severity and key pathophysiologic features, including elevated serum IgE, epidermal hyperplasia, and mast cell infiltration. In vitro, PGH produced broader suppression of pro-inflammatory outputs, reducing cytokine release in keratinocytes and attenuating NO production and iNOS expression in macrophages under inflammatory challenge. Across models, the enhanced activity of PGH was associated with reduced TLR4 abundance and attenuation of NF-kappa B pathway activation, consistent with dampened inflammatory mediator production. Collectively, these findings support HME processing as a scalable strategy to enhance PG-derived anti-inflammatory activity in dermatitis models and provide a mechanistic basis for formulation-dependent efficacy.

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