Germershaus, Oliver

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Germershaus
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Oliver
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Germershaus, Oliver

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2015 - 2019102020 - 20243

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Gerade angezeigt 1 - 10 von 13
  • Vorschaubild
    Publikation
    Comparison of protein-like model particles fabricated by micro 3D printing to established standard particles
    (Elsevier, 08/2024) Amara, Ilias; Germershaus, Oliver; Lentes, Christopher; Sass, Steffen; Youmto, Stephany Mamdjo; Stracke, Jan Olaf; Clemens-Hemmelmann, Mirjam; Assfalg, Anacelia
    Innovative analytical instruments and development of new methods has provided a better understanding of protein particle formation in biopharmaceuticals but have also challenged the ability to obtain reproducible and reliable measurements. The need for protein-like particle standards mimicking the irregular shape, translucent nature and near-to-neutral buoyancy of protein particles remained one of the hot topics in the field of particle detection and characterization in biopharmaceutical formulations. An innovative protein-like particle model has been developed using two photo polymerization (2PP) printing allowing to fabricate irregularly shaped particles with similar properties as protein particles at precise size of 50 µm and 150 µm, representative of subvisible particles and visible particles, respectively. A study was conducted to compare the morphological, physical, and optical properties of artificially generated protein particles, polystyrene spheres, ETFE, and SU-8 particle standards, along with newly developed protein-like model particles manufactured using 2PP printing. Our results suggest that 2PP printing can be used to produce protein-like particle standards that might facilitate harmonization and standardization of subvisible and visible protein particle characterization across laboratories and organizations.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Vorschaubild
    Publikation
    Enzymatic degradation pattern of polysorbate 20 impacts interfacial properties of monoclonal antibody formulations
    (Elsevier, 01/2024) Gregoritza, Kathrin; Theodorou, Christos; Heitz, Marc; Graf, Tobias; Germershaus, Oliver; Gregoritza, Manuel
    Polysorbate 20 (PS20) is widely used to maintain protein stability in biopharmaceutical formulations. However, PS20 is susceptible to hydrolytic degradation catalyzed by trace amounts of residual host cell proteins present in monoclonal antibody (mAb) formulations. The resulting loss of intact surfactant and the presence of PS20 degradation products, such as free fatty acids (FFAs), may impair protein stability. In this study, two hydrolytically-active immobilized lipases, which primarily targeted either monoester or higher-order ester species in PS20, were used to generate partially-degraded PS20. The impact of PS20 degradation pattern on critical micelle concentration (CMC), surface tension, interfacial rheology parameters and agitation protection was assessed. CMC was slightly increased upon monoester degradation, but significantly increased upon higher-order ester degradation. The PS20 degradation pattern also significantly impacted the dynamic surface tension of a mAb formulation, whereas changes in the equilibrium surface tension were mainly caused by the adsorption of FFAs onto the air-water interface. In an agitation protection study, monoester degradation resulted in the formation of soluble mAb aggregates and proteinaceous particles, suggesting that preferential degradation of PS20 monoester species can significantly impair mAb stability. Additional mAbs should be tested in the future to assess the impact of the protein format.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Kein Vorschaubild vorhanden
    Publikation
    Not the usual suspects. Alternative surfactants for biopharmaceuticals
    (American Chemical Society, 2023) Brosig, Sebastian; Cucuzza, Stefano; Serno, Tim; Bechtold-Peters, Karoline; Buecheler, Jakob; Zivec, Matej; Germershaus, Oliver; Gallou, Fabrice
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Kein Vorschaubild vorhanden
    Publikation
    A Versatile Biocompatible Antibiotic Delivery System Based on Self‐Assembling Peptides with Antimicrobial and Regenerative Potential
    (Wiley, 15.04.2019) Koch, Franziska; Kilian, David; Hettich, Timm; Germershaus, Oliver
    Periodontitis is a chronic inflammatory and tissue‐destructive disease. Since the polymicrobiome in the oral cavity makes it difficult to treat, novel therapeutic strategies are required. Hydrogels based on self‐assembling peptides (SAP) can be suitable candidates for periodontal therapy due to their injectability, biocompatibility, cargo‐loading capacity, and tunable physicochemical and mechanical properties. In this study, two SAP hydrogels (P11‐4 and P11‐28/29) are examined for their intrinsic antimicrobial activity, regenerative potential, and antibiotic delivery capacity. A significant antibacterial effect of P11‐28/29 hydrogels on the periodontal pathogen Porphyromonas gingivalis and a less pronounced effect for P11‐4 hydrogels is demonstrated. The metabolic activity rates of human dental follicle stem cells (DFSCs), which reflect cell viability and may thus indicate the regenerative capacity, are similar on tissue culture polystyrene (TCPS) and on P11‐4 hydrogels after 14 days of culture. Noticeably, both SAP hydrogels strengthen the osteogenic differentiation of DFSCs compared with TCPS. The incorporation of tetracycline, ciprofloxacin, and doxycycline does not affect fibril formation of either SAP hydrogel and results in favorable release kinetics up to 120 h. In summary, this study reveals that P11‐SAP hydrogels combine many favorable properties required to make them applicable as prospective novel treatment strategy for periodontal therapy.
    01A - Beitrag in wissenschaftlicher Zeitschrift
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    Publikation
    06 - Präsentation
  • Kein Vorschaubild vorhanden
    Publikation
    Matrix Metalloprotease Triggered Bioresponsive Drug Delivery Systems–Design, Synthesis and Application
    (Elsevier, 10/2018) Nultsch, Kira; Germershaus, Oliver
    Engineering of drug delivery systems has evolved in recent decades from comparably simple designs that merely controlled drug release to complex, often multistage systems that respond to multiple biological or environmental stimuli. Matrix metalloproteases (MMPs) are a family of proteolytic enzymes that are involved in numerous physiologic and pathophysiologic processes, including cancer. Therefore, these enzymes represent highly relevant targets for the development of novel bioresponsive drug delivery systems. The first part of this review summarizes major developments of the various types of MMP responsive drug delivery systems that have been achieved in the last decade and highlights promising strategies. The selection and incorporation of MMP sensitive elements into drug delivery systems as well as the interaction between MMP, drug delivery system and drug require additional scrutiny to avoid common pitfalls. Thus, the second part of this review focusses on strategies for successful selection and incorporation of MMP sensitive elements and on important design parameters related to the drug delivery system and the drug. This review will therefore provide a broad overview of successful MMP-sensitive drug delivery system designs and will inform about important design criteria for novel systems.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Kein Vorschaubild vorhanden
    Publikation
    Effects of Silk Degumming Process on Physicochemical, Tensile, and Optical Properties of Regenerated Silk Fibroin
    (Wiley, 09/2018) Nutsch, Kira; Bast, Livia K.; Näf, Muriel; El Yakhlifi, Salima; Bruns, Nico; Germershaus, Oliver
    Sericin removal from silk (degumming) affects material characteristics of silk fibroin (SF). Sodium carbonate is most commonly used for degumming, but numerous alternative methods are available. Herein, a systematic comparison of degumming methods is provided. Sodium carbonate, sodium oleate, trypsin, and ionic liquid are used, and materials are characterized regarding mass loss, SF content, molecular integrity of SF, refractive index, and tensile properties. Complete degumming is achieved within 30 min of using sodium carbonate, but results in significant reduction of molecular weight, shift toward less acidic charge variants, and reduction of yield‐ and rupture force. Sodium oleate and trypsin are inefficient and negatively affect tensile properties, while ionic liquid shows good efficiency and marginal degradation of SF but also reduced yield‐ and rupture force. Refractive index is not affected by degumming. These results allow rational selection of the degumming method and tuning of SF properties for biomedical applications.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Kein Vorschaubild vorhanden
    Publikation
    Container Closure Integrity Testing of Prefilled Syringes,
    (Elsevier, 08/2018) Pelaez, Sarah; Mahler, Hanns-Christian; Koulov, Atanas; Singh, Satish K.; Germershaus, Oliver; Mathaes, Roman
    Prefilled syringes (PFSs) are increasingly preferred over vials as container closure systems (CCSs) for injectable drug products when facilitated or self-administration is required. However, PFSs are more complex compared to CCSs consisting of vial, rubber stopper, and crimp cap. Container closure integrity (CCI) assurance and verification has been a specific challenge for PFSs as they feature several sealing areas. A comprehensive understanding of the CCS is necessary for an appropriate CCI assessment as well as for packaging development and qualification. A comprehensive CCI assessment of 6 different PFSs from 3 different manufacturers (including 1 polymeric PFS) was conducted using helium leak testing. PFS components were manipulated to systematically assess the contribution of the different sealing areas to CCI, namely rigid needle shield (RNS)/needle, RNS/tip cone, and the individual ribs of a syringe plunger. The polymeric PFS required an equilibrium measurement for accurate container closure integrity testing. The different sealing areas and a single plunger rib were shown to provide adequate CCI. Acceptable tip cap movement until the point of CCI failure was estimated. The assessment of acceptable tip cap movement demonstrated the importance of considering the RNS/tip cone seal design to ensure CCI of the PFS upon post assembly possesses and shipment.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Kein Vorschaubild vorhanden
    Publikation
    Surface modification of nanofibrous matrices via layer-by-layer functionalized silk assembly for mitigating the foreign body reaction
    (Elsevier, 05/2018) Qian, Yuna; Li, Linhao; Song, Yang; Dong, Lili; Chen, Peixing; Li, Xiaoming; Cai, Kaiyong; Germershaus, Oliver; Li, Yang; Fan, Yubo
    The inherent hydrophobicity and large surface area of electrospun synthetic polymeric scaffolds often cause non-specific protein adsorption, thereby influencing macrophage functions and eventually leading to fibrosis at the tissue-scaffold interface. This work reports fabrication of silk fibroin (SF)-functionalized electrospun polycaprolactone (PCL) fibers by single-component layer-by-layer assembly and decorate the SF with heparin disaccharide (HD), resulting in the non-covalent binding of interleukin-4 (IL-4) with the capacity to modulate macrophage polarization. A modified SF derivative was obtained by diazonium coupling and then covalently bonded with HD via click chemistry to eventually bind IL-4 efficiently and maintain its bioactivity. In vitro studies showed that IL-4 surface-functionalized nanofibrous scaffolds promoted polarization to M2 macrophages in the short-term. Importantly, in a murine subcutaneous implantation model, we found that promoting transient shifts in macrophage polarization at early stage can significantly inhibit the extent of the late foreign body reactions. Furthermore, the results of a transcriptomic profiling showed that MARK, PI3K, JNK and NF-κB signaling pathways played an important role in regulating the macrophage phenotypes in the SF/HD/IL-4-functionalized fibers. Our results suggest that such a strategy offers a new approach for utilizing biological agent surface functionalization to modulate the foreign body reaction to nanofibrous scaffolds.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Kein Vorschaubild vorhanden
    Publikation
    Methods To Determine the Silicone Oil Layer Thickness in Sprayed-On Siliconized Syringes
    (Parenteral Drug Association, 05/2018) Loosli, Viviane; Germershaus, Oliver; Steinberg, Henrik; Dreher, Sascha; Grauschopf, Ulla; Funke, Stephanie
    The silicone lubricant layer in prefilled syringes has been investigated with regards to siliconization process performance, prefilled syringe functionality, and drug product attributes, such as subvisible particle levels, in several studies in the past. However, adequate methods to characterize the silicone oil layer thickness and distribution are limited, and systematic evaluation is missing. In this study, white light interferometry was evaluated to close this gap in method understanding. White light interferometry demonstrated a good accuracy of 93-99% for MgF2 coated, curved standards covering a thickness range of 115-473 nm. Thickness measurements for sprayed-on siliconized prefilled syringes with different representative silicone oil distribution patterns (homogeneous, pronounced siliconization at flange or needle side, respectively) showed high instrument (0.5%) and analyst precision (4.1%). Different white light interferometry instrument parameters (autofocus, protective shield, syringe barrel dimensions input, type of non-siliconized syringe used as base reference) had no significant impact on the measured average layer thickness. The obtained values from white light interferometry applying a fully developed method (12 radial lines, 50 mm measurement distance, 50 measurements points) were in agreement with orthogonal results from combined white and laser interferometry and 3D-laser scanning microscopy. The investigated syringe batches (lot A and B) exhibited comparable longitudinal silicone oil layer thicknesses ranging from 170-190 nm to 90-100 nm from flange to tip and homogeneously distributed silicone layers over the syringe barrel circumference (110- 135 nm). Empty break-loose (4-4.5 N) and gliding forces (2-2.5 N) were comparably low for both analyzed syringe lots. A silicone oil layer thickness of 100-200 nm was thus sufficient for adequate functionality in this particular study. Filling the syringe with a surrogate solution including short-term exposure and emptying did not significantly influence the silicone oil layer at the investigated silicone level. It thus appears reasonable to use this approach to characterize silicone oil layers in filled syringes over time. The developed method characterizes non-destructively the layer thickness and distribution of silicone oil in empty syringes and provides fast access to reliable results. The gained information can be further used to support optimization of siliconization processes and increase the understanding of syringe functionality.LAY ABSTRACT: Silicone oil layers as lubricant are required to ensure functionality of prefilled syringes. Methods evaluating these layers are limited, and systematic evaluation is missing. The aim of this study was to develop and assess white light interferometry as an analytical method to characterize sprayed-on silicone oil layers in 1 mL prefilled syringes. White light interferometry showed a good accuracy (93-99%) as well as instrument and analyst precision (0.5% and 4.1%, respectively). Different applied instrument parameters had no significant impact on the measured layer thickness. The obtained values from white light interferometry applying a fully developed method concurred with orthogonal results from 3D-laser scanning microscopy and combined white light and laser interferometry. The average layer thicknesses in two investigated syringe lots gradually decreased from 170-190 nm at the flange to 100-90 nm at the needle side. The silicone layers were homogeneously distributed over the syringe barrel circumference (110-135 nm) for both lots. Empty break-loose (4-4.5 N) and gliding forces (2-2.5 N) were comparably low for both analyzed syringe lots. Syringe filling with a surrogate solution, including short-term exposure and emptying, did not significantly affect the silicone oil layer. The developed, non-destructive method provided reliable results to characterize the silicone oil layer thickness and distribution in empty siliconized syringes. This information can be further used to support optimization of siliconization processes and increase understanding of syringe functionality.
    01A - Beitrag in wissenschaftlicher Zeitschrift