Macrophage activation through phagocytosis of muramyl dipeptide encapsulated in gelatin microspheres.

Gelatin microspheres containing muramyl dipeptide (MDP) were prepared by crosslinking with glutaraldehyde. They were added to mouse peritoneal macrophages (PMs) to potentiate the tumour growth inhibitory activity. The PMs which had internalized the microspheres exhibited growth inhibitory activity to syngeneic, allogeneic, and xenogeneic tumour cells. A similar effect was observed for PMs incubated with free MDP, but the MDP encapsulated in the microspheres was more efficient in enhancing the PM activity than the free MDP. In addition, PMs were activated in much shorter periods upon incubation with the microsphere-encapsulated MDP. The duration of activity could be controlled for up to 7 days by changing the extent of crosslinking of microspheres. Dose-response experiments established that microsphere-encapsulated MDP is able to activate PMs to inhibit growth of tumour cells at concentrations approximately 2000 times lower than the free MDP present in media. The activity of PMs was also acquired on intraperitoneal injection of the microspheres, in contrast to PMs with the free MDP.