Biophysical Studies and In Vitro Effects of Tumor Cell Lines of Cannabidiol and Its Cyclodextrin Inclusion Complexes
Kyriaki Hatziagapiou,
Kostas Bethanis,
Eleni Koniari,
Elias Christoforides,
Olti Nikola,
Athena Andreou,
Aimilia Mantzou,
George P. Chrousos,
Christina Kanaka-Gantenbein,
George I. Lambrou
Affiliations
Kyriaki Hatziagapiou
Choremeio Research Laboratory, First Department of Pediatrics, National and Kapodistrian University of Athens, Thivon & Levadeias 8, 11527 Athens, Greece
Kostas Bethanis
Physics Laboratory, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, 75 Iera Odos, 11855 Athens, Greece
Eleni Koniari
UNESCO Chair on Adolescent Health Care, “Aghia Sophia” Children’s Hospital, University Research Institute of Maternal and Child Health & Precision Medicine, National and Kapodistrian University of Athens, Thivon & Levadeias 8, 11527 Athens, Greece
Elias Christoforides
Physics Laboratory, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, 75 Iera Odos, 11855 Athens, Greece
Olti Nikola
Choremeio Research Laboratory, First Department of Pediatrics, National and Kapodistrian University of Athens, Thivon & Levadeias 8, 11527 Athens, Greece
Athena Andreou
Genetics Laboratory, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, 75 Iera Odos, 11855 Athens, Greece
Aimilia Mantzou
Choremeio Research Laboratory, First Department of Pediatrics, National and Kapodistrian University of Athens, Thivon & Levadeias 8, 11527 Athens, Greece
George P. Chrousos
UNESCO Chair on Adolescent Health Care, “Aghia Sophia” Children’s Hospital, University Research Institute of Maternal and Child Health & Precision Medicine, National and Kapodistrian University of Athens, Thivon & Levadeias 8, 11527 Athens, Greece
Christina Kanaka-Gantenbein
Choremeio Research Laboratory, First Department of Pediatrics, National and Kapodistrian University of Athens, Thivon & Levadeias 8, 11527 Athens, Greece
George I. Lambrou
Choremeio Research Laboratory, First Department of Pediatrics, National and Kapodistrian University of Athens, Thivon & Levadeias 8, 11527 Athens, Greece
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 β-CD (RM-β-CD) and 2-hyroxypropyl-β-CD (HP-β-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-β-CD (DM-β-CD) and 2,3,6-tri-O-methyl-β-CD (TM-β-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-β-CD and HP-β-CD was tested on two cell lines, the A172 glioblastoma and TE671 rhabdomyosarcoma cell lines. Methylated β-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.
