MACROPHAGE ACTIVITY MAY BE MODIFIED IN-VIVO BY GALENICAL EXCIPIENTS

Excipients present in drug formulations may have an impact on the immu ne system. We present evidence of modifications of macrophage activati on observed after administration to mice of galenical excipients commo nly used in drug manufacturing, including sugars (glucose and mannitol ), surfactants (polysorbate 80, cremophor El, egg, lecithin, pluronic F68), polysaccharides (dextran 20 and 40), and pyrogenated silica (cab osil). They were dissolved in distilled water at 0. 1 % (5% for mannit ol and glucose), and sterilized at 120-degrees-C for 20 min. Macrophag e phagocytic activity was measured in terms of chemoluminescence follo wing engulfment of opsonized zymosan. Marked macrophage recruitment to the peritoneal cavity occurred after dextran 40 and mannitol injectio n. Phagocytic activity was increased after the injection of dextran 40 , dextran 20, pluronic F68, mannitol, glucose, cremophor EL and cabosi l (in increasing order of efficiency), but not polysorbate 80.