Protein precoating of polylactide microspheres containing a lipophilic immunopotentiator for enhancement of macrophage phagocytosis and activation.

Biodegradable microspheres containing a lipophilic muramyl dipeptide, MDP-B30, were prepared from a L-lactic acid-glycolic acid copolymer. The effect of precoating the microspheres with water-soluble polymers including proteins on the antitumor activity of mouse peritoneal macrophages (M phi) was investigated. Macrophages activated by phagocytosis of the microspheres exhibited growth inhibitory activity toward Meth-A tumor cells. The activity correlated with the extent of M phi phagocytosis of the microspheres. M phi phagocytosis was greatly augmented by gelatin precoating of the microspheres, resulting in a significant increase of in vitro antitumor activity of M phi by the microspheres. However, potentiation of M phi activity by gelatin precoating was minimal after intraperitoneal injection of the microspheres, but cross-linking of the coated gelatin with glutaraldehyde afforded potentiation of the antitumor activity in vivo.