Characterization of molecular interactions between cannabidiol and human plasma proteins (serum albumin and γ-globulin) by surface plasmon resonance, microcalorimetry, and molecular docking
Document Type
Article
Date of Original Version
5-30-2022
Abstract
A cannabidiol (CBD) oral solution (Epidiolex®) has been approved by the United States Food and Drug Administration to treat seizure conditions. However, the biomedical and pharmaceutical applications of CBD are hindered partially due to a limited understanding of CBD's pharmacokinetic behaviors, such as its interactions with plasma proteins. Herein, we investigated the molecular interactions between CBD and two plasma proteins, namely, human serum albumin (HSA) and γ-globulin, using biophysical techniques including surface plasmon resonance (SPR), isothermal titration calorimetry, and differential scanning calorimetry, as well as molecular docking. CBD bound to HSA and γ-globulin in an exothermic manner (enthalpy: −9.3 ×104 and −3.7 ×104 kcal/mol, respectively) with a binding affinity of 1.8 × 10−5 and 1.3 × 10−5 M, respectively. The binding ratio between CBD and HSA or γ-globulin was approximately 1:1 and 3:1, respectively. Furthermore, computational modeling suggested that CBD and warfarin may bind to HSA independently, supported by data from a competitive SPR binding assay. Findings from the current study elucidate CBD's plasma protein binding characteristics and shed light on their impact on CBD's pharmacokinetic property.
Publication Title, e.g., Journal
Journal of Pharmaceutical and Biomedical Analysis
Volume
214
Citation/Publisher Attribution
Liu, Chang, Ang Cai, Hui-Fang Li, Ni Deng, Bongsup P. Cho, Navindra P. Seeram, and Hang Ma. "Characterization of molecular interactions between cannabidiol and human plasma proteins (serum albumin and γ-globulin) by surface plasmon resonance, microcalorimetry, and molecular docking." Journal of Pharmaceutical and Biomedical Analysis 214, (2022). doi: 10.1016/j.jpba.2022.114750.