Drug delivery using novel nanoplexes against a Salmonella mouse infection model

A novel methodology for incorporating gentamicin into macromolecular complexes with anionic homo- and block copolymers via cooperative electrostatic interactions is described. Block copolymers of poly(ethylene oxide-b-sodium acrylate) (PEO-b-PAA(-) Na+) or poly(ethylene oxide-b-sodium methacrylate) (PEO-b-PMA(-) Na+) were blended with PAA(-) Na+ and complexed with the polycationic antibiotic gentamicin. Gentamicin nanoplexes made with PEO-b-PMA(-) Na+/PAA(-) Na+ (PMPG) and analogous nanoplexes with PEO-b-PAA(-) Na+/PAA(-) Na+ (PAPG) had mean intensity average diameters of 120 and 90 nm, zeta potentials of -17 and -11 mv, and incorporated 26% and 23% by weight of gentamicin, respectively. Gentamicin release rates at physiological pH from nanoplexes were relatively slow. PAPG and PMPG as drug delivery systems for treating murine salmonellosis at doses similar to the free gentamicin experiments resulted in reduced numbers of viable bacteria in the liver and spleen. Polymeric nanoplexes developed by this methodology can potentially improve targeting of intracellular pathogens.