Intracellular Bacteria and Protozoa

MARIA JOSE MORILLA AND EDER L ROMERO

Intracellular Delivery: Fundamentals and Applications

Springer

Año: 2011; p. 1 - 63

Selecting antimicrobials as a function of their chemical structure is a classical paradigm that was challenged by the advent of nanomedicines. Drugs carried in nanoparticles can be delivered into intracellular compartments in cells from selected tissues, independently of free drug s pharmacokinetics and pharmacodynamics.Inflammation associated to most infections favors the passive targeting of intravenous or topical nanomedicines against those accessible from blood circulation or close to the skin surface, infected macrophages. As a result treatments become more selective and less toxic. Up to date however preclinical development of nanomedicines is limited to increase the targeting to infected cells. After cell uptake, drugs carried in nanoparticles are delivered to the endolysosomal pathway. The use of nanoparticles that could provide drug delivery to cell cytoplasm ? site of residence of most of the infectious targets excepting leishmania-remains unexplored. In this chapter we will survey the use of nano or microparticles as antimicrobials carriers against experimental tuberculosis, salmonellosis, tularemia, chlamydiasis, malaria, leishmaniasis, Chagas?s disease and toxoplasmosis. The inhalation of antituberculose drugs in nano and microparticles directly targets alveolar macrophages, reduces the number of administrations and provides surfactant material to atelectatic lungs. Inhalation has been the only succeeding via of administration for nanomedicines against chlamydiasis. The same as against salmonellosis and tularemia, antimycobacterial drugs loaded in intravenously administered nanoparticles effectively target extrapulmonary infected macrophages in the disseminated form of the diseases. Intravenously nanoparticles did not succeed in targeting infected erythrocytes, but were effective against infected hepatocytes in malaria. On the other hand, targets in visceral leishmaniasis are treated with intravenous nanomedicines, but the cutaneous and muco-cutaneous clinical forms need improved delivery strategies.