Nanomedicines against Infectious Diseases

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

Nanotechnology and Drug Delivery

Editorial Science Publishers

Año: 2016; p. 324 - 369

Tuberculosis, malaria, leishmaniasis and Chagas`s disease affect more than 2 billion people globally 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 attractive alternative 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 nanotechnology in the pharmaceutical and immunological field. Molecules loaded into specially designed nanoparticulate carriers can be delivered to intracellular compartments of selected tissues, enabling both targeting and physico chemical protection of drugs, with independence of their chemical structure. In other words, it is possible to modify drug´s pharmacokinetics, biodistribution and intracellular traffic of a molecule according to the structure of ad-hoc designed carriers. In the field of adjuvancy, by loading antigens within nanoparticulate carriers it is possible to modify the route of administration, raising intense and controlled immune responses, because of the preferency of antigen presenting cells of taking up particulate instead of soluble material. In particular, this chapter will survey the use of nano or microparticulate carriers as drug and vaccine delivery sistems against experimental models of tuberculosis, malaria, leishmaniasis and Chagas´s disease. The latest pre-clinical strategies showed how the inhalation of anti tuberculose drugs in nano and microparticles resulted in a direct targeting of alveolar macrophages, reducing the number of administrations and providing surfactant material to atelectatic lungs. Instead, antimalarial drugs loaded in intravenous nanoparticles did not succeed in targeting infected erythrocytes, but were effective against infected hepatocytes. Up to now, targets in visceral leishmaniasis have been efficaciously treated with intravenous nanomedicines, but the cutaneous and muco-cutaneous clinical forms need of improved delivery strategies. Chaga´s disease, with intracytoplasmic targets within nonphagocytic cells in tissues where inflammation is almost absent, remains as an unsurpassed challenge for conventional and nanomedical approaches. On the contrary, in general it is observed that micro and nano particulate adjuvants were capable of increasing the immunogenicity and the delivery of the protein or genetic material to target cells, inducing Th1 and Th2 responses, probably by affectin ginitial Ag uptake, processing and presentation. Nanoparticulate adjuvants have the potential to be stable at room temperature, stored in liquid form, presenting lower manufacturing costs than biological vaccines, thus broadening access in resource-poor areas.