Molecular Aspects of the Interaction with Gram-Negative and Gram-Positive Bacteria of Hydrothermal Carbon Nanoparticles Associated with Bac8c(2,5Leu)Antimicrobial Peptide

:antimicrobial peptides (AMPs) are widely studiedas therapeutic agents due to their broad-spectrum efficacy againstinfections. However, their clinical use is hampered by the low invivo bioavailability and systemic toxicity. Such limitations might beovercome by using appropriate drug delivery systems. Here, thepreparation of a drug delivery system (DDS) by physicalconjugation of an arginine-rich peptide and hydrothermal carbonnanoparticles (CNPs) has been explored, and its antimicrobialefficacy againstEschericia coli(E. coli) andStaphylococcus aureusinvestigated in comparison with the unloaded carrier and the freepeptide. The mechanism of interaction between CNPs and thebacteria was investigated by scanning electron microscopy and acombined dielectrophoresis-Raman spectroscopy method for real-time analysis. In view of a possible systemic administration, theeffect of proteins on the stability of the DDS was investigated by using albumin as a model protein. The peptide was boundedelectrostatically to the CNPs surface, establishing an equilibrium modulated by pH and albumin. The DDS exhibited antimicrobialactivity toward the two bacterial strains, albeit lower as compared to the free peptide. The decrease in effectiveness towardE. coliwaslikely due to the rapid formation of a particle-induced extracellular matrix. The present results are relevant for the futuredevelopment of hydrothermal CNPs as drug delivery agents of AMPs.