@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{GuentzelSchillingHanioetal.2020,
  author    = {G{\"u}ntzel, Paul and Schilling, Klaus and Hanio, Simon and Schlauersbach, Jonas and Schollmayer, Curd and Meinel, Lorenz and Holzgrabe, Ulrike},
  title     = {Bioinspired Ion Pairs Transforming Papaverine into a Protic Ionic Liquid and Salts},
  series = {ACS Omega},
  volume    = {5},
  journal   = {ACS Omega},
  number    = {30},
  doi       = {10.1021/acsomega.0c02630},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230265},
  pages     = {19202-19209},
  year      = {2020},
  abstract  = {Microbial, mammalian, and plant cells produce and contain secondary metabolites, which typically are soluble in water to prevent cell damage by crystallization. The formation of ion pairs, for example, with carboxylic acids or mineral acids, is a natural blueprint to maintain basic metabolites in solution. Here, we aim at showing whether the mostly large carboxylates form soluble protic ionic liquids (PILs) with the basic natural product papaverine resulting in enhanced aqueous solubility. The obtained PILs were characterized by H-1-N-15 HMBC nuclear magnetic resonance (NMR) and in the solid state using X-ray powder diffraction, differential scanning calorimetry, and dissolution measurements. Furthermore, their supramolecular pattern in aqueous solution was studied by means of potentiometric and photometrical solubility, NMR aggregation assay, dynamic light scattering, zeta potential, and viscosity measurements. Thereby, we identified the naturally occurring carboxylic acids, citric acid, malic acid, and tartaric acid, as being appropriate counterions for papaverine and which will facilitate the formation of PILs with their beneficial characteristics, like the improved dissolution rate and enhanced apparent solubility.},
  language  = {en}
}
@article{SchlauersbachHanioLenzetal.2021,
  author    = {Schlauersbach, Jonas and Hanio, Simon and Lenz, Bettina and Vemulapalli, Sahithya P. B. and Griesinger, Christian and P{\"o}ppler, Ann-Christin and Harlacher, Cornelius and Galli, Bruno and Meinel, Lorenz},
  title     = {Leveraging bile solubilization of poorly water-soluble drugs by rational polymer selection},
  series = {Journal of Controlled Release},
  volume    = {330},
  journal   = {Journal of Controlled Release},
  edition   = {Accepted Version},
  doi       = {10.1016/j.jconrel.2020.12.016},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296957},
  pages     = {36-48},
  year      = {2021},
  abstract  = {Poorly water-soluble drugs frequently solubilize into bile colloids and this natural mechanism is key for efficient bioavailability. We tested the impact of pharmaceutical polymers on this solubilization interplay using proton nuclear magnetic resonance spectroscopy, dynamic light scattering, and by assessing the flux across model membranes. Eudragit E, Soluplus, and a therapeutically used model polymer, Colesevelam, impacted the bile-colloidal geometry and molecular interaction. These polymer-induced changes reduced the flux of poorly water-soluble and bile interacting drugs (Perphenazine, Imatinib) but did not impact the flux of bile non-interacting Metoprolol. Non-bile interacting polymers (Kollidon VA 64, HPMC-AS) neither impacted the flux of colloid-interacting nor colloid-non-interacting drugs. These insights into the drug substance/polymer/bile colloid interplay potentially point towards a practical optimization parameter steering formulations to efficient bile-solubilization by rational polymer selection.},
  language  = {en}
}
@article{PoepplerLuebtowSchlauersbachetal.2019,
  author    = {P{\"o}ppler, Ann-Christin and L{\"u}btow, Michael M. and Schlauersbach, Jonas and Wiest, Johannes and Meinel, Lorenz and Luxenhofer, Robert},
  title     = {Loading dependent Structural Model of Polymeric Micelles Encapsulating Curcumin by Solid-State NMR Spectroscopy},
  series = {Angewandte Chemie International Edition},
  volume    = {58},
  journal   = {Angewandte Chemie International Edition},
  number    = {51},
  doi       = {10.1002/anie.201908914},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206705},
  pages     = {18540-18546},
  year      = {2019},
  abstract  = {Detailed insight into the internal structure of drug-loaded polymeric micelles is scarce, but important for developing optimized delivery systems. We observed that an increase in the curcumin loading of triblock copolymers based on poly(2-oxazolines) and poly(2-oxazines) results in poorer dissolution properties. Using solid-state NMR spectroscopy and complementary tools we propose a loading-dependent structural model on the molecular level that provides an explanation for these pronounced differences. Changes in the chemical shifts and cross-peaks in 2D NMR experiments give evidence for the involvement of the hydrophobic polymer block in the curcumin coordination at low loadings, while at higher loadings an increase in the interaction with the hydrophilic polymer blocks is observed. The involvement of the hydrophilic compartment may be critical for ultrahigh-loaded polymer micelles and can help to rationalize specific polymer modifications to improve the performance of similar drug delivery systems.},
  language  = {en}
}
@article{PoepplerLuebtowSchlauersbachetal.2019,
  author    = {P{\"o}ppler, Ann-Christin and L{\"u}btow, Michael M. and Schlauersbach, Jonas and Wiest, Johannes and Meinel, Lorenz and Luxenhofer, Robert},
  title     = {Strukturmodell von Polymermizellen in Abh{\"a}ngigkeit von der Curcumin-Beladung mithilfe von Festk{\"o}rper-NMR-Spektroskopie},
  series = {Angewandte Chemie},
  volume    = {131},
  journal   = {Angewandte Chemie},
  number    = {51},
  doi       = {10.1002/ange.201908914},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212513},
  pages     = {18712-18718},
  year      = {2019},
  abstract  = {Detaillierte Einblicke in die Struktur von mit Wirkstoffen beladenen Polymermizellen sind rar, aber wichtig um gezielt optimierte Transportsysteme entwickeln zu k{\"o}nnen. Wir konnten beobachten, dass eine Erh{\"o}hung der Curcumin-Beladung von Triblockcopolymeren auf Basis von Poly(2-oxazolinen) und Poly(2-oxazinen) schlechtere Aufl{\"o}sungseigenschaften nach sich zieht. Mitthilfe von Festk{\"o}rper-NMR-Spektroskopie und komplement{\"a}ren Techniken ist es m{\"o}glich, ein ladungsabh{\"a}ngiges Strukturmodell auf molekularer Ebene zu erstellen, das eine Erkl{\"a}rung f{\"u}r die beobachteten Unterschiede liefert. Dabei belegen die {\"A}nderungen der chemischen Verschiebungen und Kreuzsignale in 2D-NMR-Experimenten die Beteiligung des hydrophoben Polymerblocks an der Koordination der Curcumin-Molek{\"u}le, w{\"a}hrend bei h{\"o}herer Beladung auch eine zunehmende Wechselwirkung mit dem hydrophilen Polymerblock beobachtet wird. Letztere k{\"o}nnte elementar f{\"u}r die Stabilisierung von ultrahochbeladenen Polymermizellen sowie das Design von verbesserten Wirkstofftransportsystemen sein.},
  language  = {de}
}