Stimulation of nonspecific immunity, haemopoiesis and protection of mice against radiation injury by 1-adamantylamide-L-alanyl-D-isoglutamine incorporated in liposomes

1-Adamantylamide-(L)-alanyl-(D)-isoglutamine (adamantylamide dipeptide (AdD P)) belongs to a group of desmuramyl muramyl peptide derivatives which are able to protect an organism from some viral infections. Encapsulation of Ad DP to egg phosphatidyl choline liposomes and the targeting of this drug to lymphatic node macrophages via subcutaneous (s.c.) administration proved to be the efficient way to protect mice against irradiation when administered s.c., 24 h prior to lethal gamma -irradiation (long-term survival rate in the range of 40% compared with 0% in saline or free drug control). Paramete rs characteristic for the recovery of haemopoiesis in the bone marrow (numb er of granulocyte-macrophage haemopoietic progenitor cells, granulocyte-mac rophage colony forming cells (GM-CFC)) were significantly improved in compa rison with the controls iind free drug on day 10 after 6.5 Gy irradiation. The haemopoietic effect was observed in the broad application time window ( 72 h before and 48 h after irradiation). Very high radioprotective effect o f s.c. administered liposomal AdDP (L-AdDP) can be explained (together with induction of haemopoiesis) by the effective and long-lasting activation of nonspecific immunity. which withholds: tire onset of septicemia in early d ays after irradiation. Induction of nonspecific immunity was proven in Cand ida albicans infectious model. L-AdDP significantly increased both the surv ival time and score (about 40% survival compared with 0% in controls and fr ee drug). In conclusion, L-AdDP could be therapeutically beneficial to moderate the h aemopoietic damage (undesirable effect of radiotherapy or chemotherapy) and induce the non-specific immunity to support the antimicrobial treatment of immunocompromised patients (C) 2001 Elsevier Science B.V. All rights reser ved.