Characterization of molecular interactions between cannabidiol and human plasma proteins (serum albumin and γ-globulin) by surface plasmon resonance, microcalorimetry, and molecular docking.
J Pharm Biomed Anal
; 214: 114750, 2022 May 30.
Article
em En
| MEDLINE
| ID: mdl-35398615
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 11 and 31, 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canabidiol
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Pharm Biomed Anal
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos