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search.filters.applied.f.access: openAccess × Author: Koch, Marcus × End date: 2024 × Start date: 2020 × DDC: 540 × Type: article × WGL Institute: INM ×

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    Targeting extracellular lectins of Pseudomonas aeruginosa with glycomimetic liposomes
    (London [u.a.] : RSC, 2021) Metelkina, Olga; Huck, Benedikt; O'Connor, Jonathan S.; Koch, Marcus; Manz, Andreas; Lehr, Claus-Michael; Titz, Alexander
    The antimicrobial resistance crisis requires novel approaches for the therapy of infections especially with Gram-negative pathogens. Pseudomonas aeruginosa is defined as priority 1 pathogen by the WHO and thus of particular interest. Its drug resistance is primarily associated with biofilm formation and essential constituents of its extracellular biofilm matrix are the two lectins, LecA and LecB. Here, we report microbial lectin-specific targeted nanovehicles based on liposomes. LecA- and LecB-targeted phospholipids were synthesized and used for the preparation of liposomes. These liposomes with varying surface ligand density were then analyzed for their competitive and direct lectin binding activity. We have further developed a microfluidic device that allowed the optical detection of the targeting process to the bacterial lectins. Our data showed that the targeted liposomes are specifically binding to their respective lectin and remain firmly attached to surfaces containing these lectins. This synthetic and biophysical study provides the basis for future application in targeted antibiotic delivery to overcome antimicrobial resistance.
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    Crystalline Carbosilane-Based Block Copolymers: Synthesis by Anionic Polymerization and Morphology Evaluation in the Bulk State
    (Weinheim : Wiley-VCH, 2022) Hübner, Hanna; Niebuur, Bart‐Jan; Janka, Oliver; Gemmer, Lea; Koch, Marcus; Kraus, Tobias; Kickelbick, Guido; Stühn, Bernd; Gallei, Markus
    Block copolymers (BCPs) in the bulk state are known to self-assemble into different morphologies depending on their polymer segment ratio. For polymers with amorphous and crystalline BCP segments, the crystallization process can be influenced significantly by the corresponding bulk morphology. Herein, the synthesis of the amorphous-crystalline BCP poly(dimethyl silacyclobutane)-block-poly(2vinyl pyridine), (PDMSB-b-P2VP), by living anionic polymerization is reported. Polymers with overall molar masses ranging from 17 400 g to 592 200 g mol−1 and PDMSB contents of 4.8–83.9 vol% are synthesized and characterized by size-exclusion chromatography and NMR spectroscopy. The bulk morphology of the obtained polymers is investigated by means of transmission electron microscopy and small angle X-ray scattering, revealing a plethora of self-assembled structures, providing confined and nonconfined conditions. Subsequently, the influence of the previously determined morphologies and their resulting confinement on the crystallinity and crystallization behavior of PDMSB is analyzed via differential scanning calorimetry and powder X-ray diffraction. Here, fractionated crystallization and supercooling effects are observable as well as different diffraction patterns of the PDMSB crystallites for confined and nonconfined domains.
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    Synthesis and Biopharmaceutical Characterization of Amphiphilic Squalenyl Derivative Based Versatile Drug Delivery Platform
    (Lausanne : Frontiers Media, 2020) Ho, Duy-Khiet; Christmann, Rebekka; Murgia, Xabier; De Rossi, Chiara; Frisch, Sarah; Koch, Marcus; Schaefer, Ulrich F.; Loretz, Brigitta; Desmaele, Didier; Couvreur, Patrick; Lehr, Claus-Michael
    Limited drug loading capacity (LC), mostly below 5% w/w, is a significant drawback of nanoparticulate drug delivery systems (DDS). Squalenoylation technology, which employs bioconjugation of squalenyl moiety and drug, allows self-assemble of nanoparticles (NPs) in aqueous media with significantly high LC (>30% w/w). The synthesis and particle preparation of squalenoylated prodrugs are, however, not facile for molecules with multiple reactive groups. Taking a different approach, we describe the synthesis of amphiphilic squalenyl derivatives (SqDs) as well as the physicochemical and biopharmaceutical characterizations of their self-assembled NPs as DDSs. The SqDs included in this study are (i) cationic squalenyl diethanolamine (ii) PEGylated SqD (PEG 750 Da), (iii) PEGylated SqD (PEG 3,000 Da), and (iv) anionic squalenyl hydrogen sulfate. All four SqDs self-assemble into NPs in a size range from 100 to 200 nm in an aqueous solution. Furthermore, all NP derivatives demonstrate appropriate biocompatibility and adequate colloidal stability in physiological relevant pH environments. The mucoprotein binding of PEGylated NPs is reduced compared to the charged NPs. Most importantly, this technology allows excellent LC (at maximum of 45% w/w) of a wide range of multifunctional compounds, varying in physicochemical properties and molecular weight. Interestingly, the drug release profile can be tuned by different loading methods. In summary, the SqD-based NPs appear as versatile drug delivery platforms.