TY  - JOUR
A1  - Shityakov, Sergey
A1  - Förster, Carola
T1  - Pharmacokinetic Delivery and Metabolizing Rate of Nicardipine Incorporated in Hydrophilic and Hydrophobic Cyclodextrins Using Two-Compartment Mathematical Model
JF  - The Scientific World Journal
N2  - The dispersion routes of cyclodextrin complexes with nicardipine (NC), such as hydrophilic hydroxypropyl-\(\beta\)-cyclodextrin (NC/HP\(\beta\)CD) and hydrophobic triacetyl-\(\beta\)-cyclodextrin (NC/TA\(\beta\)CD), through the body for controlled drug delivery and sustained release have been examined. The two-compartment pharmacokinetic model described the mechanisms of how the human body handles with ingestion of NC-cyclodextrin complexes in gastrointestinal tract (GI), distribution in plasma, and their metabolism in the liver. The model showed that drug bioavailability was significantly improved after oral administration of cyclodextrin complexes. The mathematical significance of this study to predict nicardipine delivery using pharmacokinetic two-compartment mathematical model with linear ordinary differential equations (ODE) approach represents a valuable tool to emphasize its effectiveness and metabolizing rate and diminish the side effects.
KW  - pharmacokinetic delivery
KW  - metabolizing rate
KW  - Nicardipine
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130519
VL  - 2013
IS  - 131358
ER  - 
TY  - JOUR
A1  - Shityakov, Sergey
A1  - Broscheit, Jens
A1  - Förster, Carola
T1  - Multidrug resistance protein P-gp interaction with nanoparticles (fullerenes and carbon nanotube) to assess their drug delivery potential: a theoretical molecular docking study.
JF  - International journal of computational biology and drug design
N2  - P-glycoprotein (P-gp)-mediated efflux system plays an important role to maintain chemical balance in mammalian cells for endogenous and exogenous chemical compounds. However, despite the extensive characterisation of P-gp potential interaction with drug-like molecules, the interaction of carbon nanoparticles with this type of protein molecule is poorly understood. Thus, carbon nanoparticles were analysed, such as buckminsterfullerenes (C20, C60, C70), capped armchair single-walled carbon nanotube (SWCNT or C168), and P-gp interactions using different molecular docking techniques, such as gradient optimisation algorithm (ADVina), Lamarckian genetic algorithm (FastDock), and shape-based approach (PatchDock) to estimate the binding affinities between these structures. The theoretical results represented in this work show that fullerenes might be P-gp binders because of low levels of Gibbs free energy of binding (ΔG) and potential of mean force (PMF) values. Furthermore, the SWCNT binding is energetically unfavourable, leading to a total decrease in binding affinity by elevation of the residual area (Ares), which also affects the π-π stacking mechanisms. Further, the obtained data could potentially call experimental studies using carbon nanostructures, such as SWCNT for development of drug delivery vehicles, to administer and assess drug-like chemical compounds to the target cells since organisms probably did not develop molecular sensing elements to detect these types of carbon molecules.
KW  - SWCNT CNTs
KW  - pi-pi stacking
KW  - mean force potential
KW  - Gibbs free energy of binding
KW  - molecular docking
KW  - shape-based approach
KW  - Lamarckian genetic algorithms
KW  - gradient optimisation
KW  - drug delivery
KW  - multidrug resistance
KW  - P-glycoprotein
KW  - carbon nanoparticles
KW  - fullerenes
KW  - single-walled carbon nanotubes
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132089
VL  - 6
IS  - 4
ER  - 
TY  - JOUR
A1  - Salvador, Ellaine
A1  - Shityakov, Sergey
A1  - Förster, Carola
T1  - Glucocorticoids and endothelial cell barrier function
JF  - Cell and Tissue Research
N2  - Glucocorticoids (GCs) are steroid hormones that have inflammatory and immunosuppressive effects on a wide variety of cells. They are used as therapy for inflammatory disease and as a common agent against edema. The blood brain barrier (BBB), comprising microvascular endothelial cells, serves as a permeability screen between the blood and the brain. As such, it maintains homeostasis of the central nervous system (CNS). In many CNS disorders, BBB integrity is compromised. GC treatment has been demonstrated to improve the tightness of the BBB. The responses and effects of GCs are mediated by the ubiquitous GC receptor (GR). Ligand-bound GR recognizes and binds to the GC response element located within the promoter region of target genes. Transactivation of certain target genes leads to improved barrier properties of endothelial cells. In this review, we deal with the role of GCs in endothelial cell barrier function. First, we describe the mechanisms of GC action at the molecular level. Next, we discuss the regulation of the BBB by GCs, with emphasis on genes targeted by GCs such as occludin, claudins and VE-cadherin. Finally, we present currently available GC therapeutic strategies and their limitations.
KW  - endothelial cells
KW  - glucocorticoids
KW  - glucocorticoid receptor
KW  - blood brain barrier
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132091
VL  - 355
IS  - 3
ER  -