New aqueous dispersions of gramicidin D and poly (diallyldimethylammonium chloride): preparation, characterization and antimicrobial activity

• Ano de defesa: 2024
• Autor(a) principal: Evangelista, Marina Franchi
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Biblioteca Digitais de Teses e Dissertações da USP
• Palavras-chave em Português: Amplo espectro de atividade antimicrobiana; Antimicrobial cationic polymer; Antimicrobial peptide; Broad spectrum of antimicrobial activity; Citotoxicidade diferenciada nanopartículas Gr/PDDA; Differentiated cytotoxicity Gr/PDDA nanoparticles; Dispersão dinâmica de luz; Dynamic light scattering; Microscopia eletrônica de varredura; Peptídeo antimicrobiano; Polímero catiônico antimicrobiano; Scanning electron microscopy
• Link de acesso: https://www.teses.usp.br/teses/disponiveis/46/46136/tde-01112024-164857/

New supramolecular arrangements with antimicrobial activity represent an important alternative in the fight against multidrug-resistant microorganisms. The objective of this work was to prepare, characterize and determine the antimicrobial activity of new formulations of two agents known to be antimicrobial, but with complementary activities against Gram-negative and Gram-positive bacteria and fungi. These agents are the antimicrobial peptide gramicidin D (Gr) and the water-soluble cationic polymer poly(diallyldimethylammonium) chloride (PDDA). Aqueous dispersions of Gr were prepared and characterized, which revealed the presence of spherical nanoparticles well dispersed in the solution. When adding PDDA to Gr nanoparticles (Gr NPs), the resulting interaction was shown to be weak: despite the reversal of the zeta potential of Gr NPs, the conductivity of PDDA was not affected, indicating that its mobility in the medium remains unchanged, reflecting in the results of antimicrobial activity. Particle size distributions, mean hydrodynamic diameters (Dz), zeta potential () and polydispersity (P) were obtained by dynamic light scattering (DLS), following well-defined mathematical equations. The antimicrobial activities of Gr NPs, PDDA and Gr NPs/PDDA dispersions against the microorganisms Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans were determined by plating and viable counting. Compared to single doses of Gr, the combinations reduced the minimum microbicidal concentration (MMC) by half (S. aureus) and a quarter (C. albicans); Compared to single doses of PDDA, the combinations reduced the minimum microbicidal concentration (MMC) by 6-fold (P. aeruginosa) and 10-fold (C. albicans). The easy disaggregation between Gr NPs/PDDA favored the access of each agent to the pathogen: the PDDA anchored itself to the pathogen\'s cell wall, facilitating the insertion of Gr into the pathogen\'s cell membrane. The differential cytotoxicity of Gr NPs/PDDA suggested the possibility of new systemic uses for the combination. Aqueous dispersions of poly (methyl methacrylate) (PMMA)/ dioctadecyldimethylammonium bromide (DODAB)/ poly(diallyldimethylammonium) chloride (PDDA) nanoparticles were also evaluated in the presence of Gr NPs dispersion, yielding weak interactions between the nanostructures; these combinations still require further experiments for determining antimicrobial activity.