Application of Cannabidiol Nanoemulsion for Skin Protection Against Particulate Matter: Evidence from an Ex Vivo Human Model

Nanoemulsions (NEs) offer a promising strategy for delivering lipophilic cannabidiol (CBD) to protect skin from particulate matter (PM)-induced damage. In this study, CBD-loaded oil-in-water NEs based on Brij^® O10 (polyoxyethylene (10) oleyl ether) and olive oil were prepared by the phase inversion temperature (PIT) method and characterized. A 20% w/w Brij^® O10 formulation (B20) remained clear and stable for 30 days. CBD solubility was markedly enhanced in Brij^® O10 micelles and further increased in NEs, exceeding theoretical predictions and indicating synergistic solubilization in the oil–surfactant system. CBD incorporation lowered the PIT and induced nonlinear changes in droplet size with oil content. All formulations exhibited nanoscale droplets by dynamic light scattering and transmission electron microscopy, moderately low zeta potentials consistent with nonionic steric stabilization, and maintained physical stability despite increased turbidity at higher oil levels. In a full-thickness human ex vivo skin model exposed to PM, both blank and CBD-loaded NEs reduced interleukin-6 (IL-6) and matrix metalloproteinase-1 (MMP-1) in PM-exposed skin, with CBD-loaded NEs providing additional reductions and uniquely restoring procollagen type I C-peptide (PIP) relative to their blanks. Overall, PIT-based CBD NEs enhance CBD solubilization and protect human ex vivo skin from PM-induced inflammation and extracellular matrix degradation.