Intracellular Bacteria and Protozoa - Intracellular Delivery: Fundamentals and Applications - page 747

polyethylene glycol (PEG) hydrophilic corona) (Dos Santos et al. 2007 ). In this way,
the early capture of circulating nanoparticles by cells from the retículo endothelial
system (RES) in liver, spleen and bone marrow is diminished. Pegylated, long circu-
lating nanoparticles have increased chances of extravasation in EPR sites, where
diseased cells can be passively targeted (Fang et al. 2010 ). In the last 10 years, new
nano-objects have been designed in order to make them suitable for administration
by alternative vias to parenteral, such as mucosal and topical (Antosova et al. 2009 ;
Chadwick et al. 2010 ; Csaba et al. 2009 ). Moreover, improved knowledge has been
gained on the relationship between structure (size, shape, surface) of the nano-ob-
jects and their rate of cell capture and subsequent intracellular pathways (Decuzzi
et al. 2010 ; Ruenraroengsak et al. 2010 ). In this manner, it is in theory possible
achieve intracellular targeted drug delivery (Sahay et al. 2010 ). Classical examples
are the pH-sensitive liposomes that after cell uptake by clathrin mediated endocytosis
or phagocytosis, experience a phase transition triggered by the low pH and mas-
sively deliver their payload to the cytosol (Torchilin 2009 ). Overall nanomedicines
solve problems derived from incorrect drug targeting/selectivity. Other problems
such as poor gastrointestinal absorption and bioavailability and transient or low
maximal drug concentration in plasma, can be solved by other approaches. For
instance, micro or nanonization of drugs to increase absorption or inclusion in matri-
ces (not necessarily nano-objects) as drug depots for sustained release.
As seen in Table 1 , some intracellular bacteria survive and multiply within intra-
cytoplasmic vacuola, such as Mycobacteria and Salmonella spp . Other, such as
Lysteria, Rickketsia and Shigella escape from vacuola and cross the cytoplasm to
invade adjacent cells where reinitiate the infection cycle. Certain intracellular pro-
tozoa survive within acid intracellular compartments such as the Leishmania spp or
simply perdurate inside the cytoplasm such as Trypanosoma cruzi. Other protozoa

Table 1 Intracellular bacteria and protozoa (Kumar and Valdivia 2009 ; Maurin and Raoult 1997 )
Bacteria Cell type infected Subcellular localization

Afilia felis Macrophage, vascular

endothelial cells

Phagosome

Anaplasma phagocytophilum Neutrophil Vacuole

Brucella abortus Macrophage Vacuole

Bartonella bacilliformis Erythrocyte/endotelial cell Vacuole

Burkholderia pseudomallei Macrophage Vacuole

Calymmatobacterium granulomatosis Monocyte Vacuole

Chlamydia trachomatis Mucosal epithelial cell Vacuole

Coxiella burnetti Macrophage Phagolysosome without

alkalinization

Ehrlichia canis Neutrophile/monocyte Phagosome

Franciscella tularensis Macrophage Phagosome

Legionella pneumophila Macrophage Vacuole

Lysteria monocytogenes Macrophage/hepatocyte Cytoplasm

Mycobacterium tuberculosis,M. avium Macrophage Vacuole

Mycobacterium leprae Macrophage/schwann cell Vacuole

(continued)