Abstract
THERAPEUTIC EFFICACY OF CHLOROQUINE IN LONG CIRCULATING LIPOSOME FORMULATIONS AGAINST CHLOROQUINE-RESISTANT PLASMODIUM BERGHEI INFECTION IN MICE.

Vinoth Rajendran*, Gulam Mustafa Hasan, Neeraj Kumar, Suparna Dutt, Neha Garg, Pooja Tiwari and Prahlad C. Ghosh

ABSTRACT

Malarial parasites are developing resistance to chloroquine, the most commonly used antimalarial drug. Here, we have developed an improved long circulating liposome drug delivery vehicle for delivery of chloroquine to treat chloroquine resistant malaria in mice model. The enhancement of antiplasmodial activity was highly dependent on the size, lipid composition and presence of distearoyl phosphatidylethanolamine-methoxy-polyethylene glycol 2000 (DSPE-mPEG-2000) on liposome surface. Chloroquine in Polyethylene glycol (PEG) containing liposomal formulations exhibited spherical shape with size ranging from 80 to 100 nanometer, as measured by dynamic light scattering (DLS) and high-resolution electron microscopy (HRTEM). Chloroquine (CQ) in long circulating liposome formulations with 5mol% DSPE-mPEG 2000 resulted in enhanced killing of blood parasites compared with similar dose of free chloroquine. Compared with free drug, liposomal formulations showed enhanced efficacy assessed by clearance of parasitemia and significant delay in death of mice with Plasmodium berghei CQ-resistant infections. To our knowledge, this is the first report to demonstrate that chloroquine in Polyethylene glycol liposomal formulations can act as a chemotherapeutic agent against chloroquine resistant malaria.

Keywords: liposomal chloroquine; PEG-liposome; erythrocytes; Plasmodium berghei.


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