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.
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.
Peeters
P A
PA
Department of Pharmaceutics, Faculty of Pharmacy, University of Utrecht, The Netherlands.
Brunink
B G
BG
Eling
W M
WM
Crommelin
D J
DJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002738:Chloroquine / Q000008:administration & dosage* / Q000627:therapeutic use; D004910:Erythrocyte Membrane / Q000276:immunology; D004912:Erythrocytes / Q000469:parasitology; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage; D000922:Immunotoxins; D008081:Liposomes; D008288:Malaria / Q000188:drug therapy*; D010962:Plasmodium berghei; D051381:Rats
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D000922:Immunotoxins; D008081:Liposomes; D002738:Chloroquine