Macrophage Specific Drug Delivery in Experimental Leishmaniasis

Abstract

Macrophage-specific delivery systems are the subject of much interest nowadays, because of the fact that macrophages act as host cells for many parasites and bacteria, which give rise to outbreak of so many deadly diseases(eg. leishmaniasis, tuberculosis etc.) in humans. To combat these deadly diseases initially macrophage specific liposomal delivery system were thought of and tested in vivo against experimental leishmaniasis in hamsters using a series of indigenous or synthetic antileishmanial compounds and the results were critically discussed. In vitro testing was also done against macrophages infected with Leishmania donovani, the causative agent for visceral leishmaniasis. The common problem of liposome therapy being their larger size, stability and storage, non-ionic surfactant vesicles, niosomes were prepared, for their different drug distribution and release characteristics compared to liposomes. When tested in vivo, the retention capacity of niosomes was found to be higher than that of liposomes due to the absence of lipid molecules and their smaller size. Thus the therapeutic efficacy of certain antileishmanial compounds was found to be better than that in the liposomal form. The niosomes, being cheaper, less toxic, biodegradable and non-immunogenic, were considered for sometime as suitable alternatives to liposomes as drug carriers. Besides the advent of other classical drugs carriers(e.g. neoglycoproteins), the biggest challenge came from polymeric delivery vehicles, specially the polymeric nanoparticles which were made of cost effective biodegradable polymers and different natural polymers. Because of very small size and highly stable nature, use of nanoparticles as effective drug carriers has been explored in experimental leishmaniasis using a series of antileishmanial compounds, both of indigenous and synthetic origin. The feasibility of application in vivo, when tested for biological as well as for other physicochemical parameters, the polymeric nanoparticles have turned out to be the best and thus may be projected for effective use in the clinics.

Sequential Exposure to Carbon Nanotubes and Bacteria Enhances Pulmonary Inflammation and Infectivity

“…Macrophages may be very promising targets for drug-loaded nanoparticles due to their central role in inflammation and their ability to harbor a variety of bacteria, viruses, and parasites. This sequestering of infectious agents is significant for risk of contracting a number of deadly diseases in humans, such as leishmaniasis, tuberculosis, and HIV (22,23). Special consideration, however, should be given to the inflammatory potential of drug-laden nanoparticles with SWCNT-like properties, since SWCNT may modulate the sensitivity of the body's immune responses to infections.…”

In vitro evaluation of the effectiveness and cytotoxicity of meglumine antimoniate microspheres produced by spray drying against Leishmania infantum

“…Liposomes have chiefly been studied over the last few years using different encapsulation techniques and modifying surfaces (Frezárd et al 2000;Schettini et al 2003;Tempone et al 2004). The main problems with liposomes are their larger size, stability, storage, and their parenteral administration route (Basu and Lala 2004).…”

Consequences and Therapeutic Implications of Macrophage Apoptosis in Atherosclerosis

“…22 Macrophage-specific delivery systems, including those involving macrophage-targeted photodynamic therapy, may have a role in this regard. 95,96 Finally, in mouse models, genetic manipulations that enhance macrophage apoptosis are present at birth or, in the case of bone marrow transplantation, early in atherogenesis. 51,54 These interventions can therefore affect all atherosclerotic lesions from the beginning.…”