Neutrophil activation by plasma opsonized polymeric microspheres: inhibitory effect of Pluronic F127

The phagocytosis of drug-loaded polymeric microspheres by white blood cells , such as neutrophils or mononuclear cells, represents the major clearance mechanism by which this foreign material is eliminated from the body. The p rocess of phagocytosis requires the activation of the white blood cells by the microsphere surface, followed by binding and engulfment. Phagocytosis m ay result in the removal of the microspheres from the blood or the disease site and an inflammatory response. Therefore, we have studied the level of neutrophil activation by microspheres (+/- opsonization) manufactured from various biomaterials or polymers. Polymer microspheres with equivalent size distributions were made from poly (DL-lactic acid) (PLA), poly(epsilon-cap rolactone) (PCL), poly(methyl methacrylate) (PMMA) or a 50 : 50 blend of PL A : poly(ethylene-co-vinyl acetate) (PLA : EVA). Neutrophils were isolated from human blood and activation of these cells by microspheres was measured by chemiluminescence (CL). All four types of microspheres induced only low levels of CL, however these levels were enhanced significantly if the micr ospheres were pretreated with plasma or IgG suggesting an opsonization effe ct. The adsorption of IgG or proteins from plasma was confirmed by polyacry lamide gel electrophoresis (SDS-PAGE). The poloxamer Pluronic F127 inhibite d the opsonization effect of IgG and plasma on all four types of microspher es and inhibited protein adsorption as measured by SDS-PAGE. Since neutroph il activation is part of the inflammation process in vivo, these in vitro d ata suggest that all four types of microspheres are likely to be inflammato ry if injected into body compartments containing plasma-derived fluids. Pre treatment of the microspheres with Pluronic F127 may reduce the inflammator y potential of the microspheres. (C) 2000 Elsevier Science Ltd. All rights reserved.