Balland O, Pinto-Alphandary H, Pecquet S, Andremont A, Couvreur P
Laboratoire de Pharmacie Galénique, URA CNRS 1218, Université Paris-Sud, Châtenay-Malabry, France.
J Antimicrob Chemother. 1994 Mar;33(3):509-22. doi: 10.1093/jac/33.3.509.
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.
本研究的目的是调查负载[³H]氨苄西林的聚异己基氰基丙烯酸酯纳米颗粒与感染鼠伤寒沙门氏菌的小鼠巨噬细胞（腹腔巨噬细胞和J774细胞）之间的体外相互作用。感染复数为每个巨噬细胞对应十个细菌，纳米颗粒的平均（±标准差）直径为220（±20）nm，对应氨苄西林浓度为2 g/L。未感染的J774细胞和腹腔巨噬细胞对纳米颗粒结合的[³H]氨苄西林的摄取分别比游离[³H]氨苄西林高6倍和24倍。对于感染细胞，J774细胞和腹腔巨噬细胞的摄取分别高9倍和20倍。然而，纳米颗粒结合的氨苄西林和游离氨苄西林对细胞内鼠伤寒沙门氏菌的杀菌活性没有差异。这一意外发现可能是由于细菌诱导巨噬细胞内吞噬体-溶酶体融合受到抑制，从而阻止了吞噬体内的细菌与次级溶酶体内的纳米颗粒接触。
