Innovative Strategies to Enhance the Bioavailability of Cannabidiol: Nanotechnology and Advanced Delivery Systems.

Cannabidiol (CBD), a phytocannabinoid with therapeutic potential for neurological and other conditions, faces significant challenges in bioavailability due to its low water solubility, high lipophilicity, and extensive first-pass metabolism. Researchers have developed advanced nanodelivery systems addressing these limitations to enhance CBD's absorption, stability, and efficacy. This review provides not only a comprehensive summary of current nanotechnological delivery strategies for CBD, including nanoemulsions, liposomes, polymeric micelles, nanosuspensions, and cyclodextrin inclusion complexes, but also introduces a distinct comparative and integrative perspective. Unlike previous reviews, our work synthesizes preclinical and clinical evidence while highlighting the novel integration of nanotechnology with bioenhancers and personalized medicine approaches. We further emphasize the emerging concepts of hybrid and smart nanocarriers, which have not yet been systematically discussed, positioning them as next-generation solutions to overcome CBD's bioavailability challenges and paving the way for precision therapeutics.