Block ionomer complexes containing cationic antibiotics to kill intracellular Brucella melitensis in vitro

Brucellosis, caused by Brucella spp., is the most common zoonotic disease worldwide. It is difficult to eradicate because the pathogen resides partially within phagocytic host cells and the polar antibiotics that are recommended for treatment do not enter cells efficiently. Core‐shell block ionomer complexes (BICs) carrying antibiotics in their cores were designed to transport these drugs into cells. Polyether–polyacrylate copolymers were condensed with cationic aminoglycoside antibiotics to form BICs with diameters of 170–340 nm in water. An anionic poly(acrylate‐b‐ethylene oxide‐b‐propylene oxide‐b‐ethylene oxide‐b‐acrylate) copolymer blended with a poly(ethylene oxide‐b‐acrylate) diblock was condensed with gentamicin to afford complexes containing up to 42 wt% of the antibiotic. The poly(propylene oxide) contributed hydrophobic interactions that enhanced stability of the complexes in aqueous media, whereas the hydrophilic blocks provided a steric brush to keep the structures dispersed. In vitro efficacy of the BICs to reduce intracellular Brucella was studied in murine macrophage‐like cells. Significant bacterial reductions of 2.78 and 2.85 logs were obtained relative to only 0.75 logs for the free drug. This suggests that the BICs are efficient transporters of polar antibiotics into phagocytic cells. Copyright © 2011 John Wiley & Sons, Ltd.     

Drug delivery using novel nanoplexes against a <Emphasis Type="Italic">Salmonella</Emphasis> 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.