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Creators/Authors contains: "Tagliazucchi, Mario"

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  1. NA (Ed.)

    In recent decades, peptide amphiphiles (PAs) have established themselves as promising self-assembling bioinspired materials in a wide range of medical fields. Herein, we report a dual-therapeutic system constituted by an antimicrobial PA and a cylindrical protease inhibitor (LJC) to achieve broad antimicrobial spectrum and to enhance therapeutic efficacy. We studied two strategies: PA–LJC nanostructures (Encapsulation) and PA nanostructures + free LJC (Combination). Computational modeling using a molecular theory for amphiphile self-assembly captures and explains the morphology of PA–LJC nanostructures and the location of encapsulated LJC in agreement with transmission electron microscopy and two-dimensional (2D) NMR observations. The morphology and release profile of PA–LJC assemblies are strongly correlated to the PA:LJC ratio: high LJC loading induces an initial burst release. We then evaluated the antimicrobial activity of our nanosystems toward gram-positive and gram-negative bacteria. We found that theCombinationbroadens the spectrum of LJC, reduces the therapeutic concentrations of both agents, and is not impacted by the inoculum effect. Further, theEncapsulationprovides additional benefits including bypassing water solubility limitations of LJC and modulating the release of this molecule. The different properties of PA–LJC nanostructures results in different killing profiles, and reduced cytotoxicity and hemolytic activity. Meanwhile, details in membrane alterations caused by each strategy were revealed by various microscopy and fluorescent techniques. Last, in vivo studies in larvae treated by theEncapsulationstrategy showed better antimicrobial efficacy than polymyxin B. Collectively, this study established a multifunctional platform using a versatile PA to act as an antibiotic, membrane-penetrating assistant, and slow-release delivery vehicle.

     
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    Free, publicly-accessible full text available April 16, 2025
  2. Abstract

    The colonization of biomedical surfaces by bacterial biofilms is concerning because these microorganisms display higher antimicrobial resistance in biofilms than in liquid cultures. Developing antimicrobial coatings that can be easily applied to medically‐relevant complex‐shaped objects, such as implants and surgical instruments, is an important and challenging research direction. This work reports the preparation of antibacterial surfaces via the electrodeposition of a conformal hydrogel of self‐assembling cationic peptide‐amphiphiles (PAs). Hydrogels of three PAs are electrodeposited: C16K2, C16K3, and C18K2, where Cnis an alkyl chain ofnmethylene groups and Kmis an oligopeptide ofmlysines. The processing variables (electrodeposition time, potential, pH, salt concentration, agitation) enable fine control of film thickness, demonstrating the flexibility of the method and allowing to unravel the mechanisms underlying electrodeposition. The electrochemically prepared hydrogels inhibit the growth ofStaphylococcus aureus,Escherichia coli, andPseudomonas aeruginosain agar plates, and prevent the formation of biofilms ofAcinetobacter baumanniiandP. aeruginosaand the formation ofA. baumanniicolonies in solid media. C16K2and C16K3hydrogels outperform the antimicrobial activity of those of C18K2while maintaining good compatibility with human cells.

     
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