Valentina Laverde-Rojas1, Yamil Liscano2, Sandra Patricia Rivera-Sánchez2,3, Ivan Darío Ocampo-Ibáñez2, Yeiston Betancourt2, Maria José Alhajj4, Cristhian J Yarce4, Constain H Salamanca4, Jose Oñate-Garzón2. 1. Facultad de Salud, Programa de Medicina, Universidad Santiago de Cali, Calle 5 No. 62-00, Cali 760035, Colombia. 2. Facultad de Ciencias Básicas, Programa de Microbiología, Universidad Santiago de Cali, Calle 5 No. 62-00, Cali 760035, Colombia. 3. Laboratorio de Salud Pública Departamental, Secretaria Departamental de Salud del Valle del Cauca, Gobernación del Valle del Cauca, Cali 760045, Colombia. 4. Laboratorio de Diseño y Formulación de Productos Químicos y Derivados, Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Naturales, Universidad Icesi, Cali 760035, Colombia.
Abstract
Colistin is a re-emergent antibiotic peptide used as a last resort in clinical practice to overcome multi-drug resistant (MDR) Gram-negative bacterial infections. Unfortunately, the dissemination of colistin-resistant strains has increased in recent years and is considered a public health problem worldwide. Strategies to reduce resistance to antibiotics such as nanotechnology have been applied successfully. In this work, colistin was characterized physicochemically by surface tension measurements. Subsequently, nanoliposomes coated with highly deacetylated chitosan were prepared with and without colistin. The nanoliposomes were characterized using dynamic light scattering and zeta potential measurements. Both physicochemical parameters fluctuated relatively to the addition of colistin and/or polymer. The antimicrobial activity of formulations increased by four-fold against clinical isolates of susceptible Pseudomona aeruginosa but did not have antimicrobial activity against multidrug-resistant (MDR) bacteria. Interestingly, the free coated nanoliposomes exhibited the same antibacterial activity in both sensitive and MDR strains. Finally, the interaction of colistin with phospholipids was characterized using molecular dynamics (MD) simulations and determined that colistin is weakly associated with micelles constituted by zwitterionic phospholipids.
Colistin is a re-emergent antibiotic pan class="Chemical">peptide used as a last resort in clinical practice to overcome multi-drug resistant (MDR) Gram-negative bacterial infections. Unfortunately, the dissemination of colistin-resistant strains has increased in recent years and is considered a public health problem worldwide. Strategies to reduce resistance to antibiotics such as nanotechnology have been applied successfully. In this work, colistin was characterized physicochemically by surface tension measurements. Subsequently, nanoliposomes coated with highly deacetylated chitosan were prepared with and without colistin. The nanoliposomes were characterized using dynamic light scattering and zeta potential measurements. Both physicochemical parameters fluctuated relatively to the addition of colistin and/or polymer. The antimicrobial activity of formulations increased by four-fold against clinical isolates of susceptible Pseudomona aeruginosa but did not have antimicrobial activity against multidrug-resistant (MDR) bacteria. Interestingly, the free coated nanoliposomes exhibited the same antibacterial activity in both sensitive and MDR strains. Finally, the interaction of colistin with phospholipids was characterized using molecular dynamics (MD) simulations and determined that colistin is weakly associated with micelles constituted by zwitterionic phospholipids.
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