Chloroquine encapsulated in malaria-infected erythrocyte-specific antibody-bearing liposomes effectively controls chloroquine-resistant Plasmodium berghei infections in mice

Abstract

The suitability of liposomes as drug carriers in the treatment of drug-resistant rodent malaria was examined after covalently attaching F(ab) 2 fragments of a mouse monoclonal antibody (MAb), MAb F 10 , raised against the host cell membranes isolated from the Plasmodium berghei-infected mouse erythrocytes, to the liposome surface. The antibody-bearing liposomes thus formed specifically recognized the P. berghei-infected mouse erythrocytes under both in vitro and in vivo conditions. No such specific binding of the liposomes with the infected cells was observed when MAb F 10 was replaced by another mouse monoclonal antibody, MAb D 2 . Upon loading with the antimalarial drug chloroquine, the MAb F 10 -bearing liposomes effectively controlled not only the chloroquine-susceptible but also the chloroquine-resistant P. berghei infections in mice. The chloroquine delivered in these liposomes intravenously at a dosage of 5 mg/kg of body weight per day on days 4 and 6 postinfection completely cured the animals (75 to 90%) of chloroquine-resistant P. berghei infections. These results indicate that selective homing of chloroquine to malaria-infected erythrocytes may help to cure the chloroquine-resistant malarial infections with low doses of chloroquine.

Stearylamine Liposomal Delivery of Monensin in Combination with Free Artemisinin Eliminates Blood Stages of Plasmodium falciparum in Culture and P. berghei Infection in Murine Malaria

“…In brief, P. falciparum-infected erythrocytes (10% hematocrit and 10% parasitemia) were incubated in the presence of liposomal formulations. The uptake in erythrocytes was assessed at different time intervals (15,30,60,120, and 240 min) under asynchronous culture at 37°C. At the end of the incubation, the cells were washed twice with incomplete RPMI 1640 medium to remove unbound liposomes, and the obtained RBC pellet was resuspended in chloroform to extract intracellular fluorescence, which is released into the supernatant.…”

“…To overcome mild drug resistance, liposomes were used to deliver chloroquine for the treatment of CQ-resistant malaria (29). Liposomes bearing infected erythrocyte-specific antibodies have been used for the targeted delivery of chloroquine (30). However, no lipid-based nanoformulations for hydrophobic antimalarials have been reported.…”

Control of Malaria by Bio-Therapeutics and Drug Delivery Systems

“…The antimalarial drug CQ showed improved efficacy when delivered inside immunoliposomes targeted with the pRBC-specific monoclonal antibody BM1234 [28]. Likewise, CQ-loaded MAb F10-liposomes were able to clear not only CQ-susceptible, but also CQ-resistant parasites in mice [66]. Antibodies are glycoproteins belonging to the immunoglobulin (Ig) superfamily, and have been widely used in different biomedical applications.…”

Fungus-mediated biological synthesis of gold nanoparticles: potential in detection of liver cancer

“…To isolate LCCS antibodies specifically from the mixed population, the liver cells were brought to a single cell suspension following a published procedure 30 exploiting glutaraldehyde cross-linked stroma. This strategy led to the removal of cytosol-specific antibodies by negative selection.…”

“…To isolate the LCCS antibodies from the mixed population, the liver cells were brought into a single cell suspension and incubated with an equal volume of glutaraldehyde (6.25%) to form a stroma, following a previously published procedure standardized in our laboratory. 30 The stroma was used to remove cytosolic antigen-specific antibodies of cancer cells by negative selection. The stroma-bound LCCS antibodies were eluted using propionic acid (1 M, pH 2.4).…”