Antibody-Bearing Liposomes as Chloroquine Vehicles in Treatment of Murine Malaria

Malaria is a serious public health problem that affects about 300-500 million people and claims 1.5-2.7 million deaths every year. One-third of all humans live in zones where they risk catching it (1). The situation is aggravated because the malarial parasites are rapidly developing resistance to the existing antimalarial drugs, like chloroquine (2), when given in classical pharmaceutical forms. Studies on the molecular basis of chloroquine resistance suggest that enhanced active efflux of the drug from the cells infected with resistant parasite strain prevents drug accumulation to toxic levels within the cytosol of the infected erythrocytes (3-5). It has been shown that erythrocytes infected with chloroquine-resistant parasite accumulate less chloroquine than those with sensitive parasites (6,7). Furthermore, inhibiting the chloroquine efflux by Ca(2+)-channel blockers render the resistant cells fully sensitive to chloroquine (8), indicating that the antimalarial activity of the chloroquine is directly related to its concentration within the parasite food vacuole (9). The mechanism by which this concentration effect is achieved is unclear, but it is believed to involve binding to a putative chloroquine receptor (10).