Journal
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
Volume 214, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jpba.2022.114750
Keywords
Cannabidiol; Plasma protein; Human serum albumin; gamma-globulin; Surface plasmon resonance; Isothermal titration calorimetry; Differential scanning calorimetry
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Funding
- Rhode Island Institutional Development Award (IDeA) Network of Biomedical Research Excellence from the National Institute of General Medical Sciences of the National Institutes of Health [P20GM103430]
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This study investigated the molecular interactions between CBD and two plasma proteins, HSA and γ-globulin. The results showed that CBD bound to these proteins with an exothermic manner and had a significant binding affinity. Furthermore, computational modeling suggested that CBD and warfarin may bind to HSA independently.
A cannabidiol (CBD) oral solution (Epidiolex (R)) 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 gamma-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 gamma-globulin in an exothermic manner (enthalpy: -9.3 x10(4) and -3.7 x10(4) kcal/ mol, respectively) with a binding affinity of 1.8 x 10(-5) and 1.3 x 10(-5) M, respectively. The binding ratio between CBD and HSA or gamma-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.
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