Design and development of nanoparticles for specific targeting of antimalarial drug to plasmodium infected Red blood cells (pRBC)

Malaria is a global health priority with more than 3 billion people at risk of acquiring the disease. Treating malaria has become greatest challenge despite of all the advances in technology and innovations. The main reason for failure of the current conventional chemotherapy is development of multiple-drug resistance and non-specific targeting to intracellular parasite which result in high doses of therapeutic agents and their related toxicities.
Plasmodium strain has developed complex mechanisms for drug resistance due to mutation on the P. falciparum chloroquine transporter gene (pfcrt) and the P. falciparum multi-drug resistance gene (pfmdr 1). The concept of “magic bullets” given by Ehrilch has now metamorphosed to “magic wands”, in the form of targeted drug delivery systems. The systems are said to specifically target the required site-of-action by passive modes or with the help of active ligands attached on the nanocarrier system. The sub-micron size of various nanosystems offer excellent opportunities so that they pass through the physiological barriers and access different tissues followed by an efficient cellular uptake.
Targeting approach for malaria-infected erythrocytes using nanosystems open new doors for the treatment of the disease. The goal of the malaria therapy is targeting the infected RBCs to achieve high intra-cellular drug concentration. In order to reach the set goal the carrier system should be able to cross multiple membrane barriers to access the intraparasitic targets. Upon invasion by malaria parasite, the erythrocyte cell membrane undergoes major changes in the structure, composition and function. Since mature erythrocytes have limited synthetic capabilities, the generation and regulation of pathways responsible for molecular transport in the infected RBC are probably under parasite control. During its intraerythrocytic growth Plasmodium modifies the membrane permeability of the host cell in order to uptake nutrients from the plasma, dispose of metabolic waste. Plasmodium induces new permation pathways (NPP) that confer to the pRBC an increased permeability to a wide range of materials. Certain macromolecules like Dextran, Protein A and IgG2 antibody have shown to have direct access to the parasite. These changes are of interest from the point of view of antimalarial chemotherapy as possible routes for targeting parasiticidal drugs into the intracellular parasite.