title: Sevoflurane-Sulfobutylether-β-Cyclodextrin Complex: Preparation, Characterization, Cellular Toxicity, Molecular Modeling and Blood-Brain Barrier Transport Studies.
abstract: 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 (Papp). In addition, SEV binding affinity to SBEβCD was confirmed by a minimal Gibbs free energy of binding (ΔGbind) value of -1.727 ± 0.042 kcal·mol-1 and an average binding constant (Kb) of 53.66 ± 9.24 mM indicating rapid drug liberation from the cyclodextrin amphiphilic cavity.
authors.affiliation: Department of Anaesthesia and Critical Care, University of Würzburg, 97080 Würzburg, Germany. E_Shityako_S@ukw.de.
authors.forename: Sergey
authors.initials: S
authors.lastname: Shityakov
authors.affiliation: CycloLab Cyclodextrin Research & Development Laboratory Ltd., H-1097 Budapest, Hungary. puskas@cyclolab.hu.
authors.forename: István
authors.initials: I
authors.lastname: Puskás
authors.affiliation: Sapiotec Ltd., 97078 Würzburg, Germany. papai@sapiotec.de.
authors.forename: Katalin
authors.initials: K
authors.lastname: Pápai
authors.affiliation: Department of Anaesthesia and Critical Care, University of Würzburg, 97080 Würzburg, Germany. Salvador_E@ukw.de.
authors.forename: Ellaine
authors.initials: E
authors.lastname: Salvador
authors.affiliation: Department of Anaesthesia and Critical Care, University of Würzburg, 97080 Würzburg, Germany. AN_Direktion@ukw.de.|Sapiotec Ltd., 97078 Würzburg, Germany. AN_Direktion@ukw.de.
authors.forename: Norbert
authors.initials: N
authors.lastname: Roewer
authors.affiliation: Department of Anaesthesia and Critical Care, University of Würzburg, 97080 Würzburg, Germany. Foerster_C@ukw.de.
authors.forename: Carola
authors.initials: C
authors.lastname: Förster
authors.affiliation: Department of Anaesthesia and Critical Care, University of Würzburg, 97080 Würzburg, Germany. papai@sapiotec.de.|Sapiotec Ltd., 97078 Würzburg, Germany. papai@sapiotec.de.
authors.forename: Jens-Albert
authors.initials: JA
authors.lastname: Broscheit
mesh_terms: D018685:Anesthetics, Inhalation / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001812:Blood-Brain Barrier / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002199:Capillary Permeability; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008738:Methyl Ethers / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D062105:Molecular Docking Simulation; D061251:Primary Cell Culture; D011433:Propranolol / Q000378:metabolism / Q000494:pharmacology; D000077149:Sevoflurane; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D018685:Anesthetics, Inhalation; D003692:Delayed-Action Preparations; D008738:Methyl Ethers; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; D000077149:Sevoflurane; D011433:Propranolol
keywords: blood-brain barrier; cyclodextrin formulations; molecular docking; molecular liphophilicity potential; primary microvascular endothelial cells; sevoflurane; sulfobutylether-β-cyclodextrin