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  - 
TY  - JOUR
A1  - Neuhaus, Winfried
A1  - Burek, Malgorzata
A1  - Djuzenova, Cholpon C
A1  - Thal, Serge C
A1  - Koepsell, Hermann
A1  - Roewer, Norbert
A1  - Förster, Carola Y
T1  - Addition of NMDA-receptor antagonist MK801 during oxygen/glucose deprivation moderately attenuates the up-regulation of glucose uptake after subsequent reoxygenation in brain endothelial cells
N2  - During stroke the blood–brain barrier (BBB) is damaged which can result in vasogenic brain edema and inflammation. The reduced blood supply leads to decreased delivery of oxygen and glucose to affected areas of the brain. Oxygen and glucose deprivation (OGD) can cause upregulation of glucose uptake of brain endothelial cells. In this letter, we investigated the influence of MK801, a non-competitive inhibitor of the NMDA-receptor, on the regulation of the glucose uptake and of the main glucose transporters glut1 and sglt1 in murine BBB cell line cerebEND during OGD. mRNA expression of glut1 was upregulated 68.7- fold after 6 h OGD, which was significantly reduced by 10 μM MK801 to 28.9-fold. Sglt1 mRNA expression decreased during OGD which was further reduced by MK801. Glucose uptake was significantly increased up to 907% after 6 h OGD and was still higher (210%) after the 20 h reoxygenation phase compared to normoxia. Ten micromolar MK801 during OGD was able to reduce upregulated glucose uptake after OGD and reoxygenation significantly. Presence of several NMDAR subunits was proven on the mRNA level in cerebEND cells. Furthermore, it was shown that NMDAR subunit NR1 was upregulated during OGD and that this was inhibitable by MK801. In conclusion, the addition of MK801 during the OGD phase reduced significantly the glucose uptake after the subsequent reoxygenation phase in brain endothelial cells.
KW  - Blut-Hirn-Schranke
KW  - Schlaganfall
KW  - Glucosetransportproteine
KW  - NMDA-Antagonist
KW  - NMDA-Rezeptor
KW  - blood-brain barrier
KW  - MK801
KW  - NMDAR
KW  - stroke
KW  - glut1
KW  - sglt1
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67241
ER  -