Ex Vivo Drug Screening Assay with Artificial Membranes: Characterizing Cholesterol Desorbing Competencies of Beta-Cyclodextrins.
Langmuir
; 39(36): 12590-12598, 2023 09 12.
Article
en En
| MEDLINE
| ID: mdl-37651551
ABSTRACT
Despite advancements in contemporary therapies, cardiovascular disease from atherosclerosis remains a leading cause of mortality worldwide. Supported lipid bilayers (SLBs) are membrane interfaces that can be constructed with varying lipid compositions. Herein, we use a solvent-assisted lipid bilayer (SALB) construction method to build SLB membranes with varying cholesterol compositions to create a lipid-sterol interface atop a piezoelectric sensor. These cholesterol-laden SLBs were utilized to investigate the mechanisms of various cholesterol-lowering drug molecules. Within a flow-cell, membranes with varying cholesterol content were exposed to cyclodextrins 2-hydroxypropyl-beta-cyclodextrin (HPßCD) and methyl-beta-cyclodextrin (MßCD). Quartz-crystal microgravimetry with dissipation monitoring (QCM-D) enabled the collection of in vitro, real-time changes in relative areal mass and dissipation. We define the cholesterol desorbing competency of a cyclodextrin species via measures of the rate of cholesterol removal, the rate of the transfer of membrane-bound cholesterol to drug-complexed cholesterol, and the binding strength of the drug to the cholesterol-ladened membrane. Desorption data revealed distinct cholesterol removal kinetics for each cyclodextrin while also supporting a model for the lipid-cholesterol-drug interface. We report that MßCD removes a quantity of cholesterol 1.61 times greater, with a speed 2.12 times greater, binding affinity to DOPC lipid interfaces 1.97 times greater, and rate of internal cholesterol transfer 3.41 times greater than HPßCD.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ciclodextrinas
/
Beta-Ciclodextrinas
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Idioma:
En
Revista:
Langmuir
Asunto de la revista:
QUIMICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos