Biophysical Studies and In Vitro Effects of Tumor Cell Lines of Cannabidiol and Its Cyclodextrin Inclusion Complexes

Phytocannabinoids possess anticancer properties, as established in vitro and in vivo. However, they are characterized by high lipophilicity. To improve the properties of cannabidiol (CBD), such as solubility, stability, and bioavailability, CBD inclusion complexes with cyclodextrins (CDs) might be employed, offering targeted, faster, and prolonged CBD release. The aim of the present study is to investigate the in vitro effects of CBD and its inclusion complexes in randomly methylated beta-CD (RM-beta-CD) and 2-hyroxypropyl-beta-CD (HP-beta-CD). The enhanced solubility of CBD upon complexation with CDs was examined by phase solubility study, and the structure of the inclusion complexes of CBD in 2,6-di-O-methyl-beta-CD (DM-beta-CD) and 2,3,6-tri-O-methyl-beta-CD (TM-beta-CD) was determined by X-ray crystallography. The structural investigation was complemented by molecular dynamics simulations. The cytotoxicity of CBD and its complexes with RM-beta-CD and HP-beta-CD was tested on two cell lines, the A172 glioblastoma and TE671 rhabdomyosarcoma cell lines. Methylated beta-CDs exhibited the best inclusion ability for CBD. A dose-dependent effect of CBD on both cancer cell lines and improved efficacy of the CBD-CDs complexes were verified. Thus, cannabinoids may be considered in future clinical trials beyond their palliative use as possible inhibitors of cancer growth.

Automated summary

Phytocannabinoids, such as CBD, have anticancer properties, but their high lipophilicity limits their solubility, stability, and bioavailability. This study investigates the in vitro effects of CBD and its inclusion complexes with cyclodextrins (CDs) on cancer cell lines. The study demonstrates that CBD complexed with methylated beta-CDs exhibits enhanced solubility and improved efficacy against cancer cells, suggesting the potential of cannabinoids as inhibitors of cancer growth.