The uptake of ampicillin-loaded nanoparticles by murine macrophages infected with Salmonella typhimurium

Abstract

The purpose of this study was to investigate the in-vitro interaction between [³H]ampicillin-loaded polyisohexylcyanoacrylate nanoparticles and murine macrophages (peritoneal and J774) infected with Salmonella typhimurium. The multiplicity of infection was ten bacteria to each macrophage and the mean (±s.d.) diameter of the nanoparticles was 220(±20 nm), corresponding to an ampicillin concentration of 2 g/L. The uptake of nanoparticle-bound [³H]ampicillin by non-infected J774 and peritoneal macrophages was six- and 24-fold greater respectively than that of free [³H]ampicillin. For infected cells, uptake by J774 and peritoneal macrophages was nine- and 20-fold greater respectively. However, there was no difference between nanoparticle-bound ampicillin and free ampicillin in terms of bactericidal activity against intracellular S. typhimurium. This unexpected observation might be accounted for by bacterium-induced inhibition of phagosome-lyosome fusion within the macrophages, thereby preventing contact between the bacteria in the phagosomes and the nanoparticles in the secondary lysosomes.