Therapeutic effect of chloroquine(CQ)-containing immunoliposomes in rats infected with Plasmodium berghei parasitized mouse red blood cells: comparison with combinations of antibodies and CQ or liposomal CQ

• Published in: Biochimica et biophysica acta Vol. 981; no. 2; p. 269
• Main Authors: Peeters, P A, Brunink, B G, Eling, W M, Crommelin, D J
• Format: Journal Article
• Language: English
• Published: Netherlands 06.06.1989
• Subjects: Animals; Antibodies, Monoclonal - therapeutic use; Chloroquine - administration & dosage; Chloroquine - therapeutic use; Erythrocyte Membrane - immunology; Erythrocytes - parasitology; Immunoglobulin Fab Fragments - administration & dosage; Immunotoxins; Liposomes; Malaria - drug therapy; Plasmodium berghei; Rats
• ISSN: 0006-3002; 1878-2434
• DOI: 10.1016/0005-2736(89)90037-0

The potential therapeutic application of chloroquine-containing immunoliposomes (Fab'-lipCQ) in a Plasmodium berghei malaria model was studied. Extending a previously described in vivo model (Peeters et al. (1988) Biochim. Biophys. Acta 943, 137-147) it was demonstrated that injection of antimouse red blood cell (anti-mRBC) Fab'-lipCQ was significantly more effective than liposome-encapsulated chloroquine (lipCQ) or free chloroquine in delaying or preventing a patent infection after intravenous injection of parasitized mouse red blood cells (p-mRBC) in rats. The results could be improved by injecting synchronized infected cells instead of non-synchronous p-mRBC in order to minimize the presence of free parasites which could easily infect rat RBC. It was further demonstrated that sequential injection of anti-mRBC IgG and lipCQ or chloroquine resulted in complete inactivation of the injected parasitized cells while Fab'-lipCQ administration resulted in a maximum score of 50% at an equal chloroquine, protein and phospholipid dose. In this report the potential of the concept of drug targeting for the effective treatment of a disease, which manifests in blood cells, was demonstrated.