TY  - JOUR
A1  - Pornsawad, Pornsarp
A1  - Sapsakul, Nantawan
A1  - Böckmann, Christine
T1  - A modified asymptotical regularization of nonlinear ill-posed problems
JF  - Mathematics
N2  - In this paper, we investigate the continuous version of modified iterative Runge–Kutta-type methods for nonlinear inverse ill-posed problems proposed in a previous work. The convergence analysis is proved under the tangential cone condition, a modified discrepancy principle, i.e., the stopping time T is a solution of ∥𝐹(𝑥𝛿(𝑇))−𝑦𝛿∥=𝜏𝛿+ for some 𝛿+>𝛿, and an appropriate source condition. We yield the optimal rate of convergence.
KW  - nonlinear operator
KW  - regularization
KW  - discrepancy principle
KW  - asymptotic method
KW  - optimal rate
Y1  - 2019
U6  - https://doi.org/10.3390/math7050419
SN  - 2227-7390
VL  - 7
PB  - MDPI
CY  - Basel, Schweiz
ET  - 5
ER  - 
TY  - JOUR
A1  - Rancan, Fiorenza
A1  - Volkmann, Hildburg
A1  - Giulbudagian, Michael
A1  - Schumacher, Fabian
A1  - Stanko, Jessica Isolde
A1  - Kleuser, Burkhard
A1  - Blume-Peytavi, Ulrike
A1  - Calderon, Marcelo
A1  - Vogt, Annika
T1  - Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels
JF  - Pharmaceutics : Molecular Diversity Preservation International
N2  - Polyglycerol-based thermoresponsive nanogels (tNGs) have been shown to have excellent skin hydration properties and to be valuable delivery systems for sustained release of drugs into skin. In this study, we compared the skin penetration of tacrolimus formulated in tNGs with a commercial 0.1% tacrolimus ointment. The penetration of the drug was investigated in ex vivo abdominal and breast skin, while different methods for skin barrier disruption were investigated to improve skin permeability or simulate inflammatory conditions with compromised skin barrier. The amount of penetrated tacrolimus was measured in skin extracts by liquid chromatography tandem-mass spectrometry (LC-MS/MS), whereas the inflammatory markers IL-6 and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). Higher amounts of tacrolimus penetrated in breast as compared to abdominal skin or in barrier-disrupted as compared to intact skin, confirming that the stratum corneum is the main barrier for tacrolimus skin penetration. The anti-proliferative effect of the penetrated drug was measured in skin tissue/Jurkat cells co-cultures. Interestingly, tNGs exhibited similar anti-proliferative effects as the 0.1% tacrolimus ointment. We conclude that polyglycerol-based nanogels represent an interesting alternative to paraffin-based formulations for the treatment of inflammatory skin conditions.
KW  - tacrolimus formulation
KW  - nanogels
KW  - skin penetration
KW  - drug delivery
KW  - human excised skin
KW  - Jurkat cells
Y1  - 2019
U6  - https://doi.org/10.3390/pharmaceutics11080394
SN  - 1999-4923
VL  - 11
IS  - 8
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Kotthoff, Lisa
A1  - Lisec, Jan
A1  - Schwerdtle, Tanja
A1  - Koch, Matthias
T1  - Prediction of transformation products of monensin by electrochemistry compared to microsomal assay and hydrolysis
JF  - Molecules
N2  - The knowledge of transformation pathways and identification of transformation products (TPs) of veterinary drugs is important for animal health, food, and environmental matters. The active agent Monensin (MON) belongs to the ionophore antibiotics and is widely used as a veterinary drug against coccidiosis in broiler farming. However, no electrochemically (EC) generated TPs of MON have been described so far. In this study, the online coupling of EC and mass spectrometry (MS) was used for the generation of oxidative TPs. EC-conditions were optimized with respect to working electrode material, solvent, modifier, and potential polarity. Subsequent LC/HRMS (liquid chromatography/high resolution mass spectrometry) and MS/MS experiments were performed to identify the structures of derived TPs by a suspected target analysis. The obtained EC-results were compared to TPs observed in metabolism tests with microsomes and hydrolysis experiments of MON. Five previously undescribed TPs of MON were identified in our EC/MS based study and one TP, which was already known from literature and found by a microsomal assay, could be confirmed. Two and three further TPs were found as products in microsomal tests and following hydrolysis, respectively. We found decarboxylation, O-demethylation and acid-catalyzed ring-opening reactions to be the major mechanisms of MON transformation.
KW  - transformation products
KW  - monensin
KW  - veterinary drugs
KW  - electrochemistry
KW  - hydrolysis
KW  - LC/HRMS
Y1  - 2019
U6  - https://doi.org/10.3390/molecules24152732
SN  - 1420-3049
VL  - 24
IS  - 15
PB  - MDPI
CY  - Basel
ER  -