Structure-Property Relations for Drug Loaded Polymer Micelles using Detailed Structural Information from Solid-State NMR Spectroscopy and Complementary Techniques
Analytical Chemistry
Final Report Abstract
In this project, polymer-drug formulations were analysed via NMR spectroscopy in the solid state as well as in biorelevant solutions. In a first step, a set of structure-property relations could be extracted. For the guest molecules, specific functional moieties were identified whose absence is detrimental to the preparation of reasonably loaded formulations. At the same time, the experiments showed that polymer structures composed of three blocks (ABA) are more suitable matrix materials than the corresponding polymers with only two blocks (AB). On top of that, relevant information for the preparation and stability upon storage could be obtained: A higher temperature during preparation has a negative impact on the long-term stability of the formulations. Storing these samples requires the absence of humidity, which is crucial to both the starting materials and the final formulation. Investigations in biorelevant liquids, which mimic human intestinal fluids, show that the drug or guest molecules in the formulations are released to the environment. Furthermore, the data highlight that apart from the often-discussed drug-drug interactions in pharmaceutical products, drug-polymer interactions should also be considered. This is especially important for elderly patients with chronic conditions, who take multiple drug products simultaneously.
Publications
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Concentration and composition dependent aggregation of Pluronic- and Poly-(2-oxazolin)-Efavirenz formulations in biorelevant media. Journal of Colloid and Interface Science, 606, 1179-1192.
Endres, Sebastian; Karaev, Emil; Hanio, Simon; Schlauersbach, Jonas; Kraft, Christian; Rasmussen, Tim; Luxenhofer, Robert; Böttcher, Bettina; Meinel, Lorenz & Pöppler, Ann-Christin
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You cannot fight the pressure: Structural rearrangements of active pharmaceutical ingredients under magic angle spinning. Magnetic Resonance in Chemistry, 60(6), 572-582.
Scheidel, Sebastian; Östreicher, Laurina; Mark, Isabelle & Pöppler, Ann‐Christin
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Structural Investigation on How Guest Loading of Poly(2-oxazoline)-Based Micelles Affects the Interaction with Simulated Intestinal Fluids. ACS Biomaterials Science & Engineering, 9(8), 4821-4830.
Endres, Sebastian; Ehrmanntraut, Silvia; Endres, Lukas; Can, Koray; Kraft, Christian; Rasmussen, Tim; Luxenhofer, Robert; Böttcher, Bettina; Engels, Bernd & Pöppler, Ann-Christin
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Unraveling an Alternative Mechanism in Polymer Self-Assemblies: An Order–Order Transition with Unusual Molecular Interactions between Hydrophilic and Hydrophobic Polymer Blocks. ACS Nano, 17(7), 6932-6942.
Hahn, Lukas; Zorn, Theresa; Kehrein, Josef; Kielholz, Tobias; Ziegler, Anna-Lena; Forster, Stefan; Sochor, Benedikt; Lisitsyna, Ekaterina S.; Durandin, Nikita A.; Laaksonen, Timo; Aseyev, Vladimir; Sotriffer, Christoph; Saalwächter, Kay; Windbergs, Maike; Pöppler, Ann-Christin & Luxenhofer, Robert
