Improved Epidermal Bioavailability and Anti-Inflammatory Activity of Cannabidiol Encapsulated in Polypeptide-Stabilised Emulsions

Cannabidiol (CBD) is a promising bioactive compound for skin applications; however, its topical delivery is limited by poor aqueous solubility, high lipophilicity, and chemical instability. Here, a polypeptide-stabilised oil-in-water emulsion enabling CBD encapsulation (ENC-CBD) was developed as an innovative delivery system to enhance the epidermal bioavailability and biological activity of CBD. Stable 216 nm ENC-CBD containing 175 mg/mL CBD exhibited long-term physicochemical stability over 18 months, maintaining CBD content, viscosity, density, and particle size within predefined specifications. Cytocompatibility studies in human keratinocytes (HaCaT) and dermal fibroblasts (HDF) showed concentration-dependent effects, with excellent biocompatibility at 1.75 mg/mL. In UVB-irradiated cellular models, ENC-CBD significantly reduced IL-6 and IL-8 production by 93% and 73%, respectively. Moreover, in reconstructed human epidermal tissues, ENC-CBD was non-irritant and achieved markedly greater epidermal CBD accumulation than non-encapsulated CBD, reaching approximately 11- and 7-fold higher levels after 6 h and 24 h, respectively. ENC-CBD applied to skin models significantly attenuated UV-induced inflammation characterised by overexpression of IL-6, IL-8, IL-1B, and TNF genes, while the delivery system appeared to have, to some extent, some anti-inflammatory properties. Overall, polypeptide-based emulsion carrier enhanced CBD epidermal delivery and its anti-inflammatory activity, highlighting its potential as a topical ingredient for skin inflammation.