Nanomedicines against Infectious diseases

EDER L ROMERO, MARIA J MORILLA, LH HIGA, AP PEREZ, P SCHILRREFF

Nanotechnology and Drug Delivery

Science Publishers

Año: 2013;

Tuberculosis, malaria, leishmaniasis and Chagas?s disease affect more than 2 billion peopleglobally and cause substantial morbidity and mortality, particularly among the world´s poorest people.The morbility and mortality of these diseases is increased on patients infected with HIV. An attractivealternative to the urgent need of developing new medication that do not generate resistence, and resultless toxic and more effective than current treatments, is offered by the intervention of nanotechnologyin the pharmaceutical and immunological field. Molecules loaded into specially designednanoparticulate carriers can be delivered to intracellular compartments of selected tissues, enablingboth targeting and physico chemical protection of drugs, with independence of their chemicalstructure. In other words, it is possible to modify drug´s pharmacokinetics, biodistribution andintracellular traffic of a molecule according to the structure of ad-hoc designed carriers. In the field ofadjuvancy, by loading antigens within nanoparticulate carriers it is possible to modify the route ofadministration, raising intense and controlled immune responses, because of the preferency of antigenpresenting cells of taking up particulate instead of soluble material. In particular, this chapter willsurvey the use of nano or microparticulate carriers as drug and vaccine delivery sistems againstexperimental models of tuberculosis, malaria, leishmaniasis and Chagas?s disease.The latest pre-clinical strategies showed how the inhalation of anti tuberculose drugs in nanoand microparticles resulted in a direct targeting of alveolar macrophages, reducing the number ofadministrations and providing surfactant material to atelectatic lungs. Instead, antimalarial drugsloaded in intravenous nanoparticles did not succeed in targeting infected erythrocytes, but wereeffective against infected hepatocytes. Up tp now, targets in visceral leishmaniasis have beenefficaciously treated with intravenous nanomedicines, but the cutaneous and muco-cutaneous clinicalforms need of improved delivery strategies. Chagas?s disease, with intracytoplasmic targets within nonphagocytic cells in tissues where inflammation is almost absent, remains as an unsurpassed challengefor conventional and nanomedical approaches. On the contrary, in general it is observed that microand nano particulate adjuvants were capable of increasing the immunogenicity and the delivery of theprotein or genetic material to target cells, inducing Th1 and Th2 responses, probably by affectinginitial Ag uptake, processing and presentation. Nanoparticulate adjuvants have the potential to bestable at room temperature, stored in liquid form, presenting lower manufacturing costs than biologicalvaccines, thus broadening access in resource-poor areas.