Cannabidiol/hydroxypropyl-β-cyclodextrin inclusion complex: structure analysis, release behavior, permeability, and bioactivity under in vitro digestion

Abstract

Cannabidiol (CBD), a natural phenolic compound, has many promising biological activities, but its use in food or other fields is restricted owing to inferior water solubility. So hydroxypropyl-β-cyclodextrin (HP-β-CD) was selected to form the inclusion complex (IC) of CBD to improve its solubility. The results showed CBD/HP-β-CD IC was formed at a 1 : 1 molar ratio. The complexation was spontaneous, endothermic, and entropy-driven. The loading efficiency (LE) and complexation efficiency (CE) were 16.2% and 95.1%, respectively. NMR revealed CBD/HP-β-CD IC was formed through incorporating the benzene ring of CBD into the HP-β-CD cavity. The water solubility was greatly enhanced to 9.4 μg mL⁻¹. About 80% of CBD molecules in the IC were released in simulated intestinal juice. The permeability, radical scavenging ability, and in vitro cytotoxicity of CBD were enhanced significantly after complexation. And the radical scavenging ability of digested IC was less potent compared with undigested IC but still stronger than that of CBD.