@article{SchlauersbachHanioRaschigetal.2022,
  author    = {Schlauersbach, Jonas and Hanio, Simon and Raschig, Martina and Lenz, Bettina and Scherf-Cavel, Oliver and Meinel, Lorenz},
  title     = {Bile and excipient interactions directing drug pharmacokinetics in rats},
  series = {European Journal of Pharmaceutics and Biopharmaceutics},
  volume    = {178},
  journal   = {European Journal of Pharmaceutics and Biopharmaceutics},
  edition   = {accepted version},
  doi       = {10.1016/j.ejpb.2022.07.016},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296969},
  pages     = {65-68},
  year      = {2022},
  abstract  = {Bile solubilization plays a major role in the absorption of poorly water-soluble drugs. Excipients used in oral drug formulations impact bile-colloidal properties and their molecular interactions. Polymer-induced changes of bile colloids, e.g., by Eudragit E, reduced the flux of the bile interacting drug Perphenazine whereas bile non-interacting Metoprolol was not impacted. This study corroborates these in vitro findings in rats. Eudragit E significantly reduced systemic availability of Perphenazine but not Metoprolol compared to the oral administrations without polymer. This study confirms the necessity to carefully select polymers for bile interacting drugs whereas non-bile interacting drugs are more robust in terms of excipient choice for formulation. The perspective of bile interaction may introduce interesting biopharmaceutical leverage for better performing oral formulations of tomorrow.},
  language  = {en}
}
@article{MasotaOhlsenSchollmayeretal.2022,
  author    = {Masota, Nelson E. and Ohlsen, Knut and Schollmayer, Curd and Meinel, Lorenz and Holzgrabe, Ulrike},
  title     = {Isolation and characterization of galloylglucoses effective against multidrug-resistant strains of Escherichia coli and Klebsiella pneumoniae},
  series = {Molecules},
  volume    = {27},
  journal   = {Molecules},
  number    = {15},
  issn      = {1420-3049},
  doi       = {10.3390/molecules27155045},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286179},
  year      = {2022},
  abstract  = {The search for new antibiotics against multidrug-resistant (MDR), Gram-negative bacteria is crucial with respect to filling the antibiotics development pipeline, which is subject to a critical shortage of novel molecules. Screening of natural products is a promising approach for identifying antimicrobial compounds hosting a higher degree of novelty. Here, we report the isolation and characterization of four galloylglucoses active against different MDR strains of Escherichia coli and Klebsiella pneumoniae. A crude acetone extract was prepared from Paeonia officinalis Linnaeus leaves, and bioautography-guided isolation of active compounds from the extract was performed by liquid-liquid extraction, as well as open column, flash, and preparative chromatographic methods. Isolated active compounds were characterized and elucidated by a combination of spectroscopic and spectrometric techniques. In vitro antimicrobial susceptibility testing was carried out on E. coli and K. pneumoniae using 2 reference strains and 13 strains hosting a wide range of MDR phenotypes. Furthermore, in vivo antibacterial activities were assessed using Galleria mellonella larvae, and compounds 1,2,3,4,6-penta-O-galloyl-β-d-glucose, 3-O-digalloyl-1,2,4,6-tetra-O-galloyl-β-d-glucose, 6-O-digalloyl-1,2,3,4-tetra-O-galloyl-β-d-glucose, and 3,6-bis-O-digalloyl-1,2,4-tri-O-galloyl-β-d-glucose were isolated and characterized. They showed minimum inhibitory concentration (MIC) values in the range of 2-256 µg/mL across tested bacterial strains. These findings have added to the number of known galloylglucoses from P. officinalis and highlight their potential against MDR Gram-negative bacteria.},
  language  = {en}
}
@article{SpangardtKesslerDobrzewskietal.2022,
  author    = {Spangardt, Christoph and Keßler, Christoph and Dobrzewski, Ramona and Tepler, Antonia and Hanio, Simon and Klaubert, Bernd and Meinel, Lorenz},
  title     = {Leveraging dissolution by autoinjector designs},
  series = {Pharmaceutics},
  volume    = {14},
  journal   = {Pharmaceutics},
  number    = {11},
  issn      = {1999-4923},
  doi       = {10.3390/pharmaceutics14112544},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297271},
  year      = {2022},
  abstract  = {Chemical warfare or terrorism attacks with organophosphates may place intoxicated subjects under immediate life-threatening and psychologically demanding conditions. Antidotes, such as the oxime HI-6, which must be formulated as a powder for reconstitution reflecting the molecule's light sensitivity and instability in aqueous solutions, dramatically improve recovery—but only if used soon after exposure. Muscle tremors, anxiety, and loss of consciousness after exposure jeopardize proper administration, translating into demanding specifications for the dissolution of HI-6. Reflecting the patients' catastrophic situation and anticipated desire to react immediately to chemical weapon exposure, the dissolution should be completed within ten seconds. We are developing multi-dose and single-dose autoinjectors to reliably meet these dissolution requirements. The temporal and spatial course of dissolution within the various autoinjector designs was profiled colorimetrically. Based on these colorimetric insights with model dyes, we developed experimental setups integrating online conductometry to push experiments toward the relevant molecule, HI-6. The resulting blueprints for autoinjector designs integrated small-scale rotor systems, boosting dissolution across a wide range of viscosities, and meeting the required dissolution specifications driven by the use of these drug products in extreme situations.},
  language  = {en}
}