Development and Characterization of a High-CBD Cannabis Extract Nanoemulsion for Oral Mucosal Delivery

The cannabidiol (CBD)-rich cannabis extract CAN296 shows anti-inflammatory and anticancer activity relevant to oral lichen planus (OLP), oral graft-versus-host disease (oGVHD), and oral squamous cell carcinoma (OSCC), but its high lipophilicity limits aqueous dispersion. This study developed a stable Tween-based nanoemulsion optimized for oral mucosal delivery. Ethanol-dissolved CAN296 was nanoemulsified using a 1% Tween/Span system. Physical stability was visually assessed; droplet size and morphology were examined by dynamic light scattering (DLS) and transmission electron microscopy (TEM); and wettability was measured by static contact angle (SCA). Additional evaluations included temperature stability (25 °C vs. 4 °C), in vitro release using a dialysis membrane, and scanning electron microscopy (SEM) of membrane-associated droplets. Nanoemulsions with ≥80% Tween 80 incorporated CAN296 up to 800 µg/mL, clear at 400 µg/mL, and uniformly turbid at 800 µg/mL. DLS and TEM confirmed spherical nanoscale droplets, and SCA indicated favorable cohesion and wettability. Stability was maintained for 30 days at 4 °C. Dialysis studies demonstrated strong membrane association with limited diffusion, supported by SEM visualization of membrane-bound droplets. The Tween-dominant (≥80%) nanoemulsion stably incorporated CAN296 up to 800 µg/mL, demonstrated nanoscale uniformity, improved 4 °C stability, and strong membrane retention under static conditions, suggesting potential for localized oral delivery.