Biomedical Engineering Reference
In-Depth Information
Intracellular Bacteria and Protozoa
Maria Jose Morilla and Eder Lilia Romero
Abstract
Selecting antimicrobials as a function of their chemical structure is a
classical paradigm that was challenged by the advent of nanomedicines. Drugs car-
ried in nanoparticles can be delivered into intracellular compartments in cells from
selected tissues, independently of free drug's pharmacokinetics and pharmacody-
namics. 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 nano-
medicines 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 resi-
dence 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 anti
tuberculose 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 nanomedi-
cines against chlamydiasis. The same as against salmonellosis and tularemia, anti-
mycobacterial 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 erythro-
cytes, 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.
M.J. Morilla and E.L. Romero (
*
)
Programa de Nanomedicinas, Departamento de Ciencia y Tecnologia,
Universidad Nacional de Quilmes, Roque Saenz Peña 180,
Bernal 1876, Buenos Aires, Argentina
e-mail: elromero@unq.edu.ar
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