Dermofunctional Vehicle Downregulates LL-37 and MMPs and Upregulates IGFBP-3.

BACKGROUND: Functional dermatological bases can contribute more than just delivery-they may actively modulate cutaneous homeostasis. Cleoderm™ is a dermofunctional base containing a patentedextract, palmitoyl tripeptide-8, bisabolol, hyaluronic acid, and functional oils, rationally designed to provide anti-inflammatory, antioxidant, and barrier-supportive properties. OBJECTIVE: To determine whether Cleoderm™ exhibits intrinsic immunomodulatory and matrix-protective effects in a physiologically relevant skin co-culture and to clarify the biomarkers most impacted, with translational relevance to acne and rosacea. METHODS: Human keratinocytes and fibroblasts were maintained in a transwell co-culture. Non-cytotoxic concentrations of Cleoderm™ (1.0% and 10.0%,) were tested with or without LPS stimulation (1 μg/mL). Viability was assessed by MTT and Trypan Blue. Cytokines (IL-6, TNF-α, IL-10, TGF-β) and MMPs (MMP-1, -3, -13) were quantified by ELISA and RT-qPCR. LL-37, IGFBP-3, and TGF-β protein levels were evaluated by Western blot. RESULTS: Cleoderm™ showed no cytotoxicity up to 10% (). It significantly reduced pro-inflammatory mediators (IL-6, TNF-α) and matrix-degrading enzymes (MMP-1, MMP-3, MMP-13) while increasing anti-inflammatory/reparative cytokines (IL-10, TGF-β). A dual, biomarker-level modulation was observed: (i) LL-37 was reduced, with a particularly pronounced decrease in secreted levels; and (ii) IGFBP-3 was markedly upregulated, indicating potential attenuation of the IGF-1 axis relevant to sebaceous lipogenesis. Collectively, these effects indicate immunoregulatory and matrix-protective activity consistent with improved cutaneous homeostasis. CONCLUSION: In a dermo-epidermally relevant in vitro model, Cleoderm™ functions as an active dermofunctional base, not merely a vehicle simultaneously tempering inflammatory signaling, preserving extracellular matrix integrity, and modulating mechanistic nodes (LL-37 and IGFBP-3) linked to rosacea and acne. These findings is consistent with the use of Cleoderm™ as a biologically supportive base for personalized compounding and justify controlled clinical evaluation.