Characterization and Differential Cytotoxicity of Gramicidin Nanoparticles Combined with Cationic Polymer or Lipid Bilayer

• Published in: Pharmaceutics 2022-09, Vol.14 (10), p.2053
• Main Authors: Pérez-Betancourt, Yunys, Zaia, Rachel, Evangelista, Marina Franchi, Ribeiro, Rodrigo Tadeu, Roncoleta, Bruno Murillo, Mathiazzi, Beatriz Ideriha, Carmona-Ribeiro, Ana Maria
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Analysis; Antibiotics; Antimicrobial agents; antimicrobial cationic lipid; antimicrobial cationic polymer; antimicrobial peptide; Bacteria; Care and treatment; Complications and side effects; Composition; Cytotoxicity; Dosage and administration; Drug delivery systems; Drug resistance in microorganisms; Drugs; Fungi; Gram-negative bacteria; Gram-positive bacteria; Health aspects; Lipids; Membrane lipids; Methods; Microscopy; Nanoparticles; Pathogens; Peptides; Physical properties; Polymers; Prevention; scanning electron microscopy; Staphylococcus aureus infections; supported cationic bilayer on silica with or without gramicidin; Vaccines; Vehicles
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics14102053

Gramicidin (Gr) nanoparticles (NPs) and poly (diallyl dimethyl ammonium) chloride (PDDA) water dispersions were characterized and evaluated against Gram-positive and Gram-negative bacteria and fungus. Dynamic light scattering for sizing, zeta potential analysis, polydispersity, and colloidal stability over time characterized Gr NPs/PDDA dispersions, and plating and colony-forming units counting determined their microbicidal activity. Cell viabilities of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans in the presence of the combinations were reduced by 6, 7, and 7 logs, respectively, at 10 μM Gr/10 μg·mL−1 PDDA, 0.5 μM Gr/0. 5μg·mL−1 PDDA, and 0.5 μM Gr/0.5 μg·mL−1 PDDA, respectively. In comparison to individual Gr doses, the combinations reduced doses by half (S. aureus) and a quarter (C. albicans); in comparison to individual PDDA doses, the combinations reduced doses by 6 times (P. aeruginosa) and 10 times (C. albicans). Gr in supported or free cationic lipid bilayers reduced Gr activity against S. aureus due to reduced Gr access to the pathogen. Facile Gr NPs/PDDA disassembly favored access of each agent to the pathogen: PDDA suctioned the pathogen cell wall facilitating Gr insertion in the pathogen cell membrane. Gr NPs/PDDA differential cytotoxicity suggested the possibility of novel systemic uses for the combination.