@phdthesis{Boehm2023,
  author    = {B{\"o}hm, Christoph},
  title     = {Thermal Stability of the Polyesters PCL and PLGA during Melt Electrowriting},
  doi       = {10.25972/OPUS-30613},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-306139},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {The focus of this thesis was to investigate how PCL and PLGA react to the heat exposure that comes with the MEW process over a defined timespan. To assess the thermal stability of PCL during MEW over 25 d, an automated collection of fibers has been used to determine the CTS on each day of heating for three different temperatures. PCL is exceptionally stable over 25 d at 75 °C, whereas for 85 °C and 95 °C a slight upward trend during the last 10 d could be observed, which is an indication for thermal degradation. Same trend could be observed for diameter of fibers produced at a fixed collector speed. For all temperatures, CTS during the first 5 d decreased due to inhomogeneities of the melt. Physical analysis of the fibers by XRD and mechanical testing showed no significant changes. To investigate the chemical details of the thermal durability, PCL was artificially aged over 25 d at 75 °C, 85 °C and 95 °C. Data from GPC analysis and rheology revealed that PCL is degrading steadily at all three temperatures. Combined with GC-MS analysis, two different mechanisms for degradation could be observed: random chain scission and unzipping. Additional GPC experiment using a mixture of PCL and a fluorescence labelled PCL showed that PCL was undergoing ester interchange reactions, which could explain its thermal stability. PLGA was established successfully as material for MEW. GPC results revealed that PLGA degraded heavily in the one-hour preheating period. To reduce the processing temperature, ATEC was blended with PLGA in three mixtures. This slowed down degradation and a processing window of 6 h could be established. Mechanical testing with fibers produced with PLGA and all three blends was performed. PLGA was very brittle, whereas the blends showed an elastic behavior. This could be explained by ester interchange reactions that formed a loosely crosslinked network with ATEC.},
  subject      = {Degradation},
  language  = {en}
}
@phdthesis{Haider2022,
  author    = {Haider, Malik Salman},
  title     = {Structure Property Relationship and Therapeutic Potential of Poly(2-oxazoline)s and Poly(2-oxazines)s based Amphiphiles},
  doi       = {10.25972/OPUS-28903},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-289036},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {In the past decade, poly(2-oxazoline)s (POx) and very recently poly(2-oxazine)s (POzi) based amphiphiles have shown great potential for medical applications. Therefore, the major aim of this thesis was to further explore the pharmaceutical and biomedical applications of POx/POzi based ABA triblock and AB diblock copolymers, respectively with the special emphasis on structure property relationship (SPR). ABA triblock copolymers (with shorter side chain length in the hydrophobic block) have shown high solubilizing capacity for hydrophobic drugs. The issue of poor aqueous solubility was initially addressed by developing a (micellar) formulation library of 21 highly diverse, hydrophobic drugs with POx/POzi based ABA triblock copolymers. Theoretically, the extent of compatibility between polymers and drug was determined by calculating solubility parameters (SPs). The SPs were thoroughly investigated to check their applicability in present systems. The selected formulations were further characterized by various physico-chemical techniques. For the biomedical applications, a novel thermoresposive diblock copolymer was synthesized which has shown promising properties to be used as hydrogel bioink or can potentially be used as fugitive support material. The most important aspect i.e. SPR, was studied with respect to hydrophilic block in either tri- or di-block copolymers. In triblock copolymer, the hydrophilic block played an important role for ultra high drug loading, while in case of diblock, it has improved the printability of the hydrogels. Apart from the basic research, the therapeutic applications of two formulations i.e. mitotane (commercially available as tablet dosage form for adrenocortical carcinoma) and BT-44 (lead compound for nerve regeneration) were studied in more detail.},
  language  = {en}
}
@phdthesis{Bozkaya2023,
  author    = {Bozkaya, Beg{\"u}m},
  title     = {Influence of Carbon Additives on the Electrochemical Performance of Modern Lead-Acid Batteries},
  doi       = {10.25972/OPUS-31917},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319174},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {In the first part of this thesis, a validation of both short-term and long-term DCA tests on 2 V laboratory cells is focussed. The aim is to improve the laboratory cell level measurement technology for dynamic charge acceptance regarding the investigation of carbon additives. To address this issue, it is crucial to apply carbon additives generating a remarkable difference in charge acceptance. For this purpose, five different carbon additives providing a variation in the specific external surface were included as additives in the negative plates of 2 V lead-acid cells. Both short-term (charge acceptance test 2 from SBA and DCA from EN) and long-term (Run-in DCA from Ford) DCA tests were executed on the lead-acid cells. Further understanding of the mechanism was studied by applying electrochemical methods like cyclic voltammetry and electrochemical impedance spectroscopy. The second part of this thesis aims to understand the impact of carbon surface functional groups on the electrochemical activity of the negative electrodes as well as the DCA of 2 V lead-acid cells. In order to address this topic, commercially available activated carbon was modified by different chemical treatments to incorporate specific surface functional groups in the carbon structure. A series of activated carbons having a broad range of pH was prepared, which were used as additives in the negative electrodes. The corresponding lead-acid cells were subjected to cyclic voltammetry and DCA test according to EN. Further, the physical and chemical properties of the functionalized carbon additives were intensively analyzed to establish a structure-property relationship with a focus on DCA.},
  subject      = {Bleiakkumulator},
  language  = {en}
}
@phdthesis{Hanio2024,
  author    = {Hanio, Simon},
  title     = {The impact of bile on intestinal permeability of drug substances},
  doi       = {10.25972/OPUS-34890},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-348906},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Most medicines are taken orally. To enter the systemic circulation, they dissolve in the intestinal fluid, cross the epithelial barrier, and pass through the liver. Intestinal absorption is driven by the unique features of the gastrointestinal tract, including the bile colloids formed in the lumen and the mucus layer covering the intestinal epithelium. Neglecting this multifaceted environment can lead to poor drug development decisions, especially for poorly water-soluble drugs that interact with bile and mucus. However, there is a lack of a rationale nexus of molecular interactions between oral medicines and gastrointestinal components with drug bioavailability. Against this background, this thesis aims to develop biopharmaceutical strategies to optimize the presentation of oral therapeutics to the intestinal epithelial barrier. In Chapter 1, the dynamics of bile colloids upon solubilization of the poorly-water soluble drug Perphenazine was studied. Perphenazine impacted molecular arrangement, structure, binding thermodynamics, and induced a morphological transition from vesicles to worm-like micelles. Despite these dynamics, the bile colloids ensured stable relative amounts of free drug substance. The chapter was published in Langmuir. Chapter 2 examined the impact of pharmaceutical polymeric excipients on bile-mediated drug solubilization. Perphenazine and Imatinib were introduced as model compounds interacting with bile, whereas Metoprolol did not. Some polymers altered the arrangement and geometry of bile colloids, thereby affecting the molecularly soluble amount of those drugs interacting with bile. These insights into the bile-drug-excipient interplay provide a blueprint to optimizing formulations leveraging bile solubilization. The chapter was published in Journal of Controlled Release. Chapter 3 deals with the impact of bile on porcine intestinal mucus. Mucus exposed to bile solution changed transiently, it stiffened, and the overall diffusion rate increased. The bile-induced changes eased the transport of the bile-interacting drug substance Fluphenazine, whereas Metoprolol was unaffected. This dichotomous pattern was linked to bioavailability in rats and generalized based on two previously published data sets. The outcomes point to a bile-mucus interaction relevant to drug delivery. The chapter is submitted. The Appendix provides a guide for biopharmaceutical characterization of drug substances by nuclear magnetic resonance spectroscopy aiming at establishing a predictive algorithm. In summary, this thesis deciphers bile-driven mechanisms shaping intestinal drug absorption. Based on these molecular insights, pharmaceuticals can be developed along a biopharmaceutical optimization, ultimately leading to better oral drugs of tomorrow.},
  subject      = {Solubilisation},
  language  = {en}
}