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  - Shityakov, Sergey
A1  - Dandekar, Thomas
A1  - Förster, Carola
T1  - Gene expression profiles and protein-protein interaction network analysis in AIDS patients with HIV-associated encephalitis and dementia
JF  - HIV/AIDS: Research and Palliative Care
N2  - Central nervous system dysfunction is an important cause of morbidity and mortality in patients with human immunodeficiency virus type 1 (HIV-1) infection and acquired immunodeficiency virus syndrome (AIDS). Patients with AIDS are usually affected by HIV-associated encephalitis (HIVE) with viral replication limited to cells of monocyte origin. To examine the molecular mechanisms underlying HIVE-induced dementia, the GSE4755 Affymetrix data were obtained from the Gene Expression Omnibus database and the differentially expressed genes (DEGs) between the samples from AIDS patients with and without apparent features of HIVE-induced dementia were identified. In addition, protein–protein interaction networks were constructed by mapping DEGs into protein–protein interaction data to identify the pathways that these DEGs are involved in. The results revealed that the expression of 1,528 DEGs is mainly involved in the immune response, regulation of cell proliferation, cellular response to inflammation, signal transduction, and viral replication cycle. Heat-shock protein alpha, class A member 1 (HSP90AA1), and fibronectin 1 were detected as hub nodes with degree values >130. In conclusion, the results indicate that HSP90A and fibronectin 1 play important roles in HIVE pathogenesis.
KW  - microarray
KW  - differentially expressed genes
KW  - protein-protein interaction network
KW  - gene ontology
KW  - encephalitis dementia
KW  - human immunodeficiency virus
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149494
VL  - 7
ER  - 
TY  - JOUR
A1  - Shityakov, Sergey
A1  - Salvador, Ellaine
A1  - Pastorin, Giorgia
A1  - Förster, Carola
T1  - Blood-brain barrier transport studies, aggregation, and molecular dynamics simulation of multiwalled carbon nanotube functionalized with fluorescein isothiocyanate
JF  - International Journal of Nanomedicine
N2  - In this study, the ability of a multiwalled carbon nanotube functionalized with fluorescein isothiocyanate (MWCNT-FITC) was assessed as a prospective central nervous system-targeting drug delivery system to permeate the blood-brain barrier. The results indicated that the MWCNT-FITC conjugate is able to penetrate microvascular cerebral endothelial monolayers; its concentrations in the Transwell® system were fully equilibrated after 48 hours. Cell viability test, together with phase-contrast and fluorescence microscopies, did not detect any signs of MWCNT-FITC toxicity on the cerebral endothelial cells. These microscopic techniques also revealed presumably the intracellular localization of fluorescent MWCNT-FITCs apart from their massive nonfluorescent accumulation on the cellular surface due to nanotube lipophilic properties. In addition, the 1,000 ps molecular dynamics simulation in vacuo discovered the phenomenon of carbon nanotube aggregation driven by van der Waals forces via MWCN-TFITC rapid dissociation as an intermediate phase.
KW  - endothelial cells
KW  - cytotoxicity
KW  - blood-brain barrier
KW  - fluorescein isothiocyanate
KW  - aggregation
KW  - molecular dynamics
KW  - fluorescence microscopy
KW  - Transwell® system
KW  - multiwalled carbon nanotube
KW  - mice
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149233
VL  - 10
ER  -