Intracellular distribution of ampicillin in murine macrophages infected with Salmonella typhimurium and treated with (3H)ampicillin-loaded nanoparticles.
The intracellular distribution of (3H)ampicillin-loaded polyisohexylcyanoacrylate nanoparticles was studied in murine macrophages (peritoneal cells and the J774 cell line) infected by Salmonella typhimurium C5, using ultrastructural autoradiography. Ampicillin penetration and retention into the cells obviously increased by means of nanoparticles. After short-term (2-4 h) treatment with the nanoparticle formulation, numerous intracellular bacteria were seen to be in the process of destruction. The tritium labelling was located in the cell cytoplasm and inside vacuoles in which bacteria undergoing degradation were often present. After long-term (12 h) treatment, numerous spherical bodies (d: 100 nm to 500 nm) and larger forms (2 microns) were seen in the vacuoles. Radioactivity was mainly found to be localized on the spherical bodies, indicating marked damaging action of the ampicillin on the bacterial walls. The targeting of ampicillin therefore allowed its penetration into the macrophages and vacuoles infected with S. typhimurium.
Balland
O
O
Laboratoire de Pharmacie Galénique, CNRS, URA 1218, Faculté de Pharmacie, Châtenay-Malabry, France.
Pinto-Alphandary
H
H
Viron
A
A
Puvion
E
E
Andremont
A
A
Couvreur
P
P
D000667:Ampicillin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D002460:Cell Line; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D010406:Penicillins / Q000493:pharmacokinetics*; D012486:Salmonella typhimurium / Q000187:drug effects*
D010406:Penicillins; D000667:Ampicillin