• The preparation process of porous starch-cannabidiol (CBD-PS) microspheres was optimized. • CBD-PS had higher stability and bioaccessibility than cannabidiol. • The in vitro anti-lung cancer mechanism of CBD-PS was preliminarily explored. Cannabidiol (CBD) is the most promising bioactive compound in industrial hemp ( Cannabis sativa L.), but its applications are limited by its poor water solubility and low bioavailability. This study used porous starch (PS) as a carrier to prepare CBD-PS microspheres, and evaluated the microspheres’ physicochemical properties, water solubility, bioavailability, and in vitro anticancer activity. Results showed that under optimal conditions (CBD concentration: 93 mg/mL; PS-to-CBD mass ratio: 4.19:1; time of load: 34 min), an encapsulation efficiency of 54.87% and a drug-loading capacity of 10.57% were achieved. CBD was encapsulated in an amorphous state within PS, and this encapsulation enhanced CBD’s thermal stability. The water solubility of CBD-PS increased by 15.99-fold compared with free CBD. Its release rate in simulated gastric fluid rose by 2.59-fold, and in simulated intestinal fluid increased by 4.41-fold. The release process followed pseudo-Fickian diffusion and first-order kinetics. CBD-PS exhibited significant inhibitory activity against A549 lung cancer cells, achieving a 52.36% inhibition rate at a concentration of 50 μg/mL. This inhibitory effect was induced by reduced mitochondrial membrane potential, along with up-regulated expression of the PPARG gene and down-regulated expression of the NQO1, HMGCR, OPRM1, and OPRD1 genes. This study provides new insights for developing novel CBD delivery systems, reveals the in vitro anticancer effects of CBD at the genetic level, and lays a theoretical foundation for the application of CBD in functional foods.
Xin et al. (Sun,) studied this question.