TY  - JOUR
A1  - Shityakov, Sergey
A1  - Puskás, István
A1  - Pápai, Katalin
A1  - Salvador, Ellaine
A1  - Roewer, Norbert
A1  - Förster, Carola
A1  - Broscheit, Jens-Albert
T1  - Sevoflurane-sulfobutylether-\(\beta\)-cyclodextrin complex: preparation, characterization, cellular toxicity, molecular modeling and blood-brain barrier transport studies
JF  - Molecules
N2  - The objective of the present investigation was to study the ability of sulfobutylether-\(\beta\)-cyclodextrin (SBECD) 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-SBE\(\beta\)CD 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 SBE\(\beta\)CD 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.
KW  - pharmaceutical applications
KW  - in vitro
KW  - propranolol
KW  - water
KW  - primary microvascular endothelial cells
KW  - molecular liphophilicity potential
KW  - molecular docking
KW  - blood-brain barrier
KW  - ulfobutylether-\(\beta\)-cyclodextrin
KW  - sevoflurane
KW  - cyclodextrin formulations
KW  - safety
KW  - etomidate
KW  - formulations
KW  - hydrochloride
KW  - ether
KW  - intestinal absorption
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148543
VL  - 20
ER  -