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

Yunys Pérez-BetancourtRachel ZaiaMarina Franchi EvangelistaRodrigo Tadeu RibeiroBruno Murillo RoncoletaBeatriz Ideriha MathiazziAna Maria Carmona-Ribeiro
Published in: Pharmaceutics (2022)
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.
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