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The diminishing portfolio of mankind's available antibiotics urges science to develop novel potent drugs. Here, we present a peptide fitting the typical blueprint of amphipathic and membrane-active antimicrobial peptides, denominated C14R. This 2 kDa peptide consists of 16 amino acid residues, with seven being either hydrophobic, aromatic, or non-polar, and nine being polar or positively charged, strictly separated on opposite sides of the predicted α-helix. The affinity of the peptide C14R to P. aeruginosa membranes and its intrinsic tendency to productively insert into membranes of such composition were analyzed by dynamic simulations. Its biological impact on the viability of two different P. aeruginosa reference strains was demonstrated by determining the minimal inhibitory concentrations (MICs), which were found to be in the range of 10–15 µg/mL. C14R's pore-forming capability was verified in a permeabilization assay based on the peptide-triggered uptake of fluorescent dyes into the bacterial cells. Finally, the peptide was used in radial diffusion assays, which are commonly used for susceptibility testing of antimicrobial peptides in clinical microbiology. In comparison to reference strains, six clinical P. aeruginosa isolates were clearly affected, thereby paving the way for further in-depth analyses of C14R as a promising new AMP drug in the future. [ABSTRACT FROM AUTHOR]

The diminishing portfolio of mankind’s available antibiotics urges science to develop novel potent drugs. Here, we present a peptide fitting the typical blueprint of amphipathic and membrane-active antimicrobial peptides, denominated C14R. This 2 kDa peptide consists of 16 amino acid residues, with seven being either hydrophobic, aromatic, or non-polar, and nine being polar or positively charged, strictly separated on opposite sides of the predicted α-helix. The affinity of the peptide C14R to P. aeruginosa membranes and its intrinsic tendency to productively insert into membranes of such composition were analyzed by dynamic simulations. Its biological impact on the viability of two different P. aeruginosa reference strains was demonstrated by determining the minimal inhibitory concentrations (MICs), which were found to be in the range of 10–15 µg/mL. C14R’s pore-forming capability was verified in a permeabilization assay based on the peptide-triggered uptake of fluorescent dyes into the bacterial cells. Finally, the peptide was used in radial diffusion assays, which are commonly used for susceptibility testing of antimicrobial peptides in clinical microbiology. In comparison to reference strains, six clinical P. aeruginosa isolates were clearly affected, thereby paving the way for further in-depth analyses of C14R as a promising new AMP drug in the future.

Herein, the micro-porous polylactic acid coating applied on the surface of the cylindrical substrate is fabricated by a novel in situ pore-formation strategy based on the combinational effect of breath figure (BF) and vapor-induced phase separation (VIPS) processes. Under the condition of high environmental humidity, solvent pair of chloroform and dimethylformamide is employed for post-treatment onto pre-formed PLA coating to induce the pore-formation following the mechanism of BF and VIPS, respectively. A composite porous structure with both cellular-like and bi-continuous network morphologies is obtained. By tunning the experimental factors including the ratio of the solvent pair, environmental humidity, and temperature, morphological manipulation upon the pore morphology can be facilely achieved based on the control of mechanism transition between BF and VIPS. Paclitaxel is used as a model drug and loaded into the porous coating by the wicking effect of post-immersion. Coatings with different morphological features show varying drug loading and release capacities. The 28-day release test reveals dynamic release profiles between different coating samples, with the total release rate ranging from 35.70% to 79.96%. Optimal loading capacity of 19.28 µg cm -2 and 28-day release rate of 35.70% are achieved for the coating with composite BF-VIPS structure. This research established a cost-efficient strategy with high flexibility in the structural manipulation concerning the construction of drug-eluting coating with the feature of manipulative drug delivery., (© 2024 Wiley‐VCH GmbH.)