Sevoflurane-Sulfobutylether-β-Cyclodextrin Complex: Preparation, Characterization, Cellular Toxicity, Molecular Modeling and Blood-Brain Barrier Transport Studies

Molecules

Sergey Shityakov²  István Puskás¹  Katalin Pápai³  Ellaine Salvador²  Norbert Roewer²  Carola Förster²  Jens-Albert Broscheit² 

[1] CycloLab Cyclodextrin Research & Development Laboratory Ltd., H-1097 Budapest, Hungary; E-Mail:;Department of Anaesthesia and Critical Care, University of Würzburg, 97080 Würzburg, Germany; E-Mails:;Sapiotec Ltd., 97078 Würzburg, Germany; E-Mail:

关键词: cyclodextrin formulations;    sevoflurane;    sulfobutylether-β-cyclodextrin;    blood-brain barrier;    primary microvascular endothelial cells;    molecular docking;    molecular liphophilicity potential;   

DOI  :  10.3390/molecules200610264

来源: mdpi

【 摘 要 】

The objective of the present investigation was to study the ability of sulfobutylether-β-cyclodextrin (SBEβCD) to form an inclusion complex with sevoflurane (SEV), a volatile anesthetic with poor water solubility. The inclusion complex was prepared, characterized and its cellular toxicity and blood-brain barrier (BBB) permeation potential of the formulated SEV have also been examined for the purpose of controlled drug delivery. The SEV-SBEβCD complex was nontoxic to the primary brain microvascular endothelial (pEND) cells at a clinically relevant concentration of sevoflurane. The inclusion complex exhibited significantly higher BBB permeation profiles as compared with the reference substance (propranolol) concerning calculated apparent permeability values (P_app). In addition, SEV binding affinity to SBEβCD was confirmed by a minimal Gibbs free energy of binding (ΔG_bind) value of −1.727 ± 0.042 kcal·mol⁻¹ and an average binding constant (K_b) of 53.66 ± 9.24 mM indicating rapid drug liberation from the cyclodextrin amphiphilic cavity.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.