Liposome-Mediated Immunosuppression Plays an Instrumental Role in the Development of “Humanized Mouse” to Study Plasmodium falciparum

Abstract

The material world has been getting prone toward infectious diseases, and therefore novel strategies should be devised to treat chronic infectious disorders. The translational biomedical research scientists made early attempts to develop mouse-human chimera (humanized mouse) through the reconstitution of immunodeficient mouse with engraftment of human cells and tissues. Although the humanized mouse proved to be an effective tool in understanding various diseases such as human malaria and hepatitis, however, drug administration, retention capacity of the administered drug, toxicity, and ethical constraints are some of the major issues and need to be objectively addressed. The "humanization" of immunodeficient mouse needs pharmacological immunomodulatory reagents to control the excessively recruited cells of monocytemacrophage lineage. Therefore, administration of liposome loaded with hydrophobic drug (clodronate) to induce selective apoptosis through "suicidal approach" in myeloid cells plays an instrumental role for controlling residual nonadaptive immune response of the host. Liposomes are spherical and hollow-structures consisting of lipid bilayer-and are used for the delivery of drug and vaccine candidates. The surfaceengineered liposomes (ligand anchored) are used for targeted and controlled delivery. Clodronate-loaded liposomes play a pivotal role in developing humanized mouse. This mouse holds relevance to study pathophysiology and immunopathology of human malaria parasite, P. falciparum. The liposomal delivery of clodronate administered in immunodeficient mice to modulate their innate immune system is an amenable strategy with the minimal/acceptable range of systemic toxicity.