Biomedical Engineering Reference
In-Depth Information
An additional difficulty with classical antibiotic therapy is that many intracellular
bacteria are quiescent or dormant. These bacteria are present in a reversible state
and can persist for extended periods without division (Kaprelyants et al.
1993
)
under a viable but non-culturable state. So the drug targets are downregulated and
the cellular permeability is altered dramatically, influencing their susceptibility to
antibacterial agents (Gilbert et al.
1990
).
On the other hand, protozoan pathogens (eukaryotic unicellular organism) like
plasmodium, leishmania, trypanosoma and toxoplasma have tremendous negative
impact on human health and prosperity. These protozoans are obligate intracellular
parasites. The intracellular habitat make possible to avoid detection and destruction
by host antibodies. As yet, there are no safe vaccines for any of these parasites,
leaving drug treatments as the major strategy for control. Available drugs are com-
promised by low efficacy, high toxicity, and wide spread resistance.
Overall, performing a strategy for passive or active drug targeting by means of
nanoparticles is far more challenging than developing a strategy for sustained drug
delivery. Tissue location of infected host cells and intracellular ubication of the
microorganism, play a protagonic role in rationale drug targeting strategies. Non
selective, widely distributed, toxic or short half live antimicrobials can be suitable
candidates for targeted delivery. Toxic antimicrobials that do not accumulate inside
the cells (Ebert
2004
) such as aminoglycosides and antibiotics that do not enter
infected intracellular compartments such as quinolonas should be candidates to
targeted delivery instead of sustained release (Hand et al.
1987
; Prokesch and Hand
1982
). Poor penetrating aminoglycosides that the same as macrolides inactivate at
low pH are candidate to early escape from endo-phagosomal pathway and delivery
against cytoplasmic microorganism. An early escape strategy is also suitable
against for agents against cytoplasmic protozoa such as
T. cruzi
and
T. gondii
. The
phagosomal via naturally culminates in delivering phagocytosed material against
Leishmania spp.
Specific targeting and intracellular delivery on erythrocytes and
hepatocytes are needed in against
Plasmodium spp
.
In this chapter we will review selected preclinical approaches that made use of
nanomedicines for intracellular delivery of antibiotic and antiprotozoal agents.
2
Mycobacterium spp
Mycobacterium tuberculosis
is a facultative intracellular pathogen, nonmotile
nonencapsulated rod shaped Gram positive aerobe (growing most successfully in
tissues with high oxygen content such as lungs) or facultative anaerobe (Godreuil
et al.
2007
).
M. tuberculosis
is the main cause of tuberculosis, a deadly infection (Kaufmann
and McMichael
2005
), considered one of the main challenges in public health
(Gaspar et al.
2008b
) Approximately two billion people (~30% of the global popu-
lation) are currently infected (The union
2008
). After HIV/AIDS, tuberculosis is
the second most deadly infectious disease (Frieden et al.
2003
), every year 9.2 million
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