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Stephan Schmidt

Stephan Schmidt

· Department Chair and the Certara Endowed Professor; Director Of The Center For Pharmacometrics And Systems PharmacologyVerified

University of Florida · Pharmaceutics

Active 1936–2026

h-index59
Citations15.9k
Papers558110 last 5y
Funding
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About

Stephan Schmidt, Ph.D., F.C.P., is associated with UF Health and is listed in the UF Health Directory. The provided page text does not include specific details about his research focus, background, or key contributions. Therefore, a detailed biography cannot be extracted from the available information.

Research topics

  • Medicine
  • Internal medicine
  • Computer Science
  • Materials science
  • Demography
  • Computational biology
  • Surgery
  • Pediatrics
  • Chromatography
  • Physics
  • Nanotechnology
  • Family medicine
  • Ecology
  • Intensive care medicine
  • Biology
  • Dentistry
  • Evolutionary biology
  • Immunology
  • Chemistry
  • Biochemistry

Selected publications

  • [18F]FDG-markierte Immunzellen als Werkzeug der vergleichenden Entzündungsbildgebung im alternativen Tiermodell Manduca sexta

    Nuklearmedizin - NuclearMedicine · 2026-04-01

    article
  • Challenging Traditional ADME Assumptions for Physiologically Based Pharmacokinetic Models for Intravenous Administration of Iron–Carbohydrate Nanomedicines: Potential Utility of Gold Nanoparticle Models as a Roadmap

    Clinical Pharmacokinetics · 2025-08-15 · 2 citations

    reviewOpen accessSenior author

    Intravenous iron-carbohydrate complexes are a class of nanomedicines that are widely used globally to treat iron deficiency and iron deficiency anemia associated with a wide spectrum of disease states. Despite being widely used in clinical practice for more than seven decades, the understanding of their in vivo disposition including tissue biodistribution and kinetics of the nanoparticle degradation at the cellular level is not well-understood. Moreover, the critical quality attributes that influence in vivo pharmacokinetics have not been fully defined. In particular, the carbohydrate moiety plays an influential role in how the nanoparticulate iron-carbohydrate complex interacts with the biological system. Developing a physiologically based pharmacokinetic (PBPK) model would facilitate a deeper understating of the key nanomedicine attributes that predict in vivo performance. Because endogenous iron metabolism complicates pharmacokinetic modeling for this complex class of drugs, models of gold nanoparticles may provide a substantive roadmap to begin to build a viable PBPK model for iron-carbohydrate nanomedicines. In the future, PBPK models that integrate recent mechanistic data regarding tissue biodistribution and intracellular iron kinetics for parameterization have the potential to improve manufacturing quality and clinical use of these complex drugs.

  • Highly Branched Sulfated Glycopolymers as Mucin Mimetics

    Journal of the American Chemical Society · 2025-08-28 · 1 citations

    articleOpen access

    Mucins are highly complex glycoproteins that form protective and lubricating barriers around epithelial surfaces, e.g., in the respiratory tract, to protect against pathogens. The isolation and purification of natural mucins without compromising their structure and thus their properties remain challenging. Glycopolymers as mucin mimetics have shown great potential in biomedical research, for example, in mucosal barrier enhancement and respiratory disease treatment, or in improving surface lubrication and adhesion properties. Here, we introduce double-brushed mucin mimetic glycopolymers, replicating for the first time a structural design that more closely imitates key architectural features of natural mucins. By combining solid-phase synthesis of sequence-defined glycooligomers and their attachment onto polyactive ester scaffolds, we enable access to a library of linear, brushed, and double-brushed glycopolymers with controlled variations of structural parameters, such as overall chain length, number, and length of branches, as well as number of carbohydrates and degree of sulfation. By using light and neutron scattering as well as atomic force microscopy-based single-molecule force spectroscopy and imaging, we can demonstrate that the double-brushed architecture is responsible for successfully mimicking critical mucin properties, such as their adhesion to hydrophilic surfaces and an extended conformation, properties that are not achieved with single-brushed or linear analogues. Thus, our findings show that double-brushed sulfated glycopolymers effectively replicate key characteristics of natural mucins, advancing their potential as mucin models, as well as for use in biomedical applications.

  • Polymer, Water, and Salt Partitioning in Complex Coacervates Characterized by Femtosecond Stimulated Raman Microscopy

    Chemistry - Methods · 2025-04-30 · 1 citations

    articleOpen access

    Complex coacervates can form through liquid–liquid phase separation in aqueous solutions containing oppositely charged macromolecules. This process results in macromolecule‐rich droplets (coacervate phase) coexisting with a macromolecule‐depleted supernatant phase. Here, femtosecond stimulated Raman microscopy (FSRM) is introduced as a tool to rapidly analyze both the supernatant and coacervate phases of complex coacervates. The well‐known polyelectrolyte pair poly(diallyldimethylammonium chloride) and poly(4‐styrenesulfonate) is investigated. Coacervate formation is induced by the addition of KBr and NH 4 SCN as a Raman‐active salt. For both salts, the partitioning of polymer and water between the coacervate droplets and the supernatant phase is quantified. For the Raman‐active salt NH 4 SCN, its partitioning between phases was also monitored. NH 4 SCN was found to be enriched in the coacervate phase, as confirmed by FTIR spectroscopy. Overall, FSRM proves to be a valuable tool for collecting new data on coacervate composition requiring only low sample volumes and simple sample preparation, while offering convenient data acquisition.

  • Sulfated Glycosaminoglycans as Inhibitors for Chlamydia Infections: Molecular Weight and Sulfation Dependence

    Macromolecular Bioscience · 2025-01-21 · 4 citations

    articleOpen accessSenior authorCorresponding

    Glycosaminoglycans (GAGs) play a pivotal role in pathogen attachment and entry into host cells, where the interaction with GAGs is critical for a diverse range of bacteria and viruses. This study focuses on elucidating the specific interactions between sulfated GAGs and the adhesin OmcB (Outer membrane complex protein B) of Chlamydia species, examining how structural characteristics of GAGs, such as sulfation degree and molecular weight, influence their binding affinity and thereby affect bacterial infectivity. A surface-based binding assay is established to determine the binding constants of OmcB with various GAGs. It is shown that increased sulfation and higher molecular weight enhance GAG binding to OmcB. These findings are further validated using cell assays, which shows that the addition of sulfated GAGs reduces OmcB-cell binding and inhibits the attachment of C. pneumoniae elementary bodies (EBs), underscoring the pivotal role of specific GAGs in chlamydial infections. Notably, heparin exhibites a stronger inhibitory effect on OmcB compare to GAGs with similar sulfation degrees and molecular weights, suggesting that particular molecular architectures may optimize binding interactions.

  • Kapitel 6: Gemeinsam die Nische verlassen

    Neue Ökologie · 2025-02-25

    book-chapterOpen access
  • Enrichment of Hyaluronic Acid Binding Tumor Cells by Modulation of Selective Adhesion on Microgel Surfaces

    Macromolecular Rapid Communications · 2025-09-24 · 1 citations

    articleOpen accessSenior authorCorresponding

    Liquid biopsy-based detection of cells with specific biomarker profiles is critical for cancer diagnostics and treatment. Here, we present a novel method for the selective enrichment of CD44-expressing tumor cells from blood using thermoresponsive microgel surfaces functionalized with hyaluronic acid (HA). A key feature of our approach is the precise modulation of CD44-HA interactions through the microgels' volume phase transition temperature (VPTT). Lowering the temperature from 37°C to 30°C induces swelling of the microgel layer, thereby diminishing adhesive interactions and promoting the detachment of weakly adhering white blood cells (WBCs), while strongly adherent tumor cells remain captured. Flow cytometry analysis studies further reveal that tumor cells with elevated CD44 expression exhibit persistent adhesion on HA-functionalized surfaces. Given the straightforward fabrication process and the versatility for incorporating various biomarkers via chemical synthesis, this temperature-responsive microgel platform holds promise for the efficient capture of circulating tumor cells (CTCs) present in the blood of cancer patients and other challenging diagnostic applications.

  • PEG-free, Triphosphate-Stabilized LNPs Enable Potent RNA Delivery

    bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-22

    articleOpen access

    ABSTRACT Polyethylene glycol (PEG)-lipids have long enabled lipid nanoparticle (LNP) formulations by providing steric stabilization and prolonged circulation. However, anti-PEG immune responses may impede repeated systemic dosing in mRNA therapeutics due to the phenomenon known as accelerated blood clearance (ABC). Here, we introduce a PEG-free, polyanionic alternative in which sodium triphosphate (3P) electrostatically associates with ionizable surface lipids, conferring long-term colloidal stability through charge repulsion rather than steric shielding. 3P-LNPs maintained size uniformity, morphology, and mRNA integrity for over nine months at 4 °C. In a proof-of-concept study involving a single intravenous injection of LNPs in mice carrying a luciferase and a GFP transgene, early expression was approximately two-fold higher compared to PEG-LNPs, while expression levels at 24 hours and hepatic tolerability remained comparable. Serum enzyme and cytokine profiles indicated no necrosis or inflammation. These findings establish 3P-LNPs as a stable, biocompatible platform free of PEG, with potential for repeat systemic mRNA administration while avoiding PEG-related effects.

  • Diacetylene‐Functionalized Glycan Mimetics for Receptor‐Mediated Cluster Imprinting in Model Membranes

    Macromolecular Rapid Communications · 2025-10-27

    articleOpen access

    The glycocalyx, a dense layer of glycoproteins and glycolipids on eukaryotic cells, is essential for cellular functions such as communication, signaling, and pathogen interactions. Certain components spontaneously organize into membrane microdomains, enhancing glycan-lectin interactions by clustering glycoproteins and glycolipids. However, studying these dynamic systems in native membranes is difficult due to their high heterogeneity. Synthetic glycocalyx mimetics have thus become valuable tools to replicate such complex interactions. In this study, we present diacetylene-containing multivalent glycomimetic ligands for integration into giant unilamellar vesicles as model membranes. We demonstrate the synthesis and application of a novel SPPoS-compatible building block that enables site-selective incorporation of a diacetylene moiety into sequence-defined, lipidated glycan mimetics. When incorporated into GUVs, the glycomimetic ligands cluster upon lectin binding, bringing diacetylene units into close proximity. UV irradiation then induces polymerization, yielding fluorescent polydiacetylene clusters that mimic receptor-mediated glycan clustering in cell membranes. This approach allows precise control over glycan cluster formation and provides a versatile platform for studying multivalent glycan-lectin interactions in clustering and membrane microdomain organization. By stabilizing glycan clusters, this system offers valuable potential for advancing our understanding of membrane-associated glycan interactions and their role in cellular signaling.

  • Real-world evidence and patient preference for subcutaneous <i>versus</i> intravenous natalizumab in the treatment of relapsing-remitting multiple sclerosis – initial results from the observational SISTER study

    Therapeutic Advances in Neurological Disorders · 2024-01-01 · 13 citations

    articleOpen access

    Background: The consideration of patient preference for a certain drug route of administration (RoA) plays an important role in promoting patient adherence in chronic diseases. Natalizumab is an established treatment for relapsing-remitting multiple sclerosis (RRMS) and can be administered as intravenous (IV) infusion or subcutaneous (SC) injection developed to enable a shorter and easier administration versus IV RoA. Study objectives: Primary objective is to compare patients’ preference for RoA and satisfaction with SC versus IV natalizumab at baseline and subsequent visits up to 12 months. Secondary objectives include drug utilization, clinical outcomes, safety, and treatment satisfaction in a usual care setting. Design and methods: SISTER (Subcutaneous: Non-Interventional Study for Tysabri Patient Preference – Experience from Real World) is an ongoing, prospective, observational study where natalizumab is utilized according to local label. RRMS patients are included in three natalizumab cohorts: Patients switching from current IV to SC administration (switcher) and patients newly starting natalizumab on either SC or IV route (starter SC/IV). This interim analysis includes 262 patients (184 switchers, 39 SC starters, and 39 IV starters), median observation period was 9 months. Results: 80.8% IV starters and 93.9% SC starters reported at baseline that they prefer the assigned RoA. Although initial satisfaction with chosen RoA was maintained over time from baseline through Month 12 in all three cohorts, the wish for change of the current RoA after 6 and 12 months was more frequently expressed among IV starters than in either SC cohort. Consistently, six patients (23.1%) starting with IV changed their RoA from IV to SC route. Mean global treatment satisfaction according to TSQM-II score at baseline remained high in the switcher group and increased through Month 12 in both IV and SC starter cohorts. Conclusion: Based on current data, there is a trend toward patients’ preference for the natalizumab SC route over the IV route, which provides valuable insights into patients’ preference for natalizumab RoA in routine care and complements available data from clinical studies with real-world data on SC natalizumab. Trial registration: This observational (non-interventional) study was registered in the local German PEI register for non-interventional studies (NIS-No. 611) and in the international CTgov register (NCT05304520).

Frequent coauthors

  • Björn Misselwitz

    Institute for Research Information and Quality Assurance

    84 shared
  • Holger Babbe

    Janssen (United States)

    81 shared
  • Reinhard Hohlfeld

    Ludwig-Maximilians-Universität München

    81 shared
  • Klaus Dornmair

    Max Planck Institute of Neurobiology

    80 shared
  • Hartmut Wekerle

    Max Planck Institute for Biological Intelligence

    80 shared
  • Günther Heller

    75 shared
  • Laura Hartmann

    University of Freiburg

    69 shared
  • Christof Veit

    64 shared
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