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

Background/Objectives: The cannabidiol (CBD)-rich cannabis extract (CAN296) exhibits potent anti-inflammatory and anticancer activity with a favorable safety profile, making it a promising candidate for the management of inflammatory, precancerous, and malignant conditions, particularly for diseases with limited treatment options such as oral lichen planus (OLP), oral manifestations of graft-versus-host disease (oGVHD), and oral squamous cell carcinoma (OSCC). However, cannabis extracts in general, including CAN296, are characterized by high lipophilicity and poor aqueous solubility, which pose significant challenges to formulation stability and bioavailability. This study aimed to develop a stable Tween-based nanoemulsion of cannabis extract optimized for oral mucosal delivery. Methods: Ethanol-dissolved cannabis extract was nanoemulsified with Tween 80/Span 80 surfactant blends at varying concentrations up to 4000 µg/mL and 1% total surfactant. Formulations were visually inspected for physical stability over an 8-week period. Selected emulsions were analyzed by dynamic light scattering (DLS) for droplet size and polydispersity and by transmission electron microscopy (TEM) for morphology. Additional assays included static contact angle (SCA) measurements for wettability, temperature-dependent stability testing (at 25 °C vs. 4 °C for 30 days), and an in vitro release study using a dialysis membrane, complemented by scanning electron microscopy (SEM) to visualize droplet deposition on the membrane surface. Results: Nanoemulsions containing ≥80% Tween 80 (1% surfactant) successfully incorporated cannabis extract up to 800 µg/mL, clear at 400 µg/mL, and turbid but homogeneous at 800 µg/mL, forming stable dispersions with improved nanoscale uniformity. DLS and TEM confirmed uniform spherical morphology, while SCA analysis indicated optimal droplet cohesion and wettability. Storage stability was maintained for 30 days at 4 °C, and in vitro dialysis studies revealed strong membrane association with limited diffusion, further supported by SEM visualization of membrane-bound aggregates. These findings suggest a favorable mucoadhesive potential for oral application. Conclusion: A Tween-dominant (≥80%) nanoemulsion stably incorporated CBD-rich extracts up to 800 µg/mL, well above therapeutic levels. The optimized system showed nanoscale uniformity, improved stability at 4 °C, and significant membrane retention, supporting its potential as a mucoadhesive platform for targeted oral delivery in immune-mediated and precancerous conditions.