Intracellular Bacteria and Protozoa - Intracellular Delivery: Fundamentals and Applications - page 791

cells, IC 50 for etanidazole was 40 mM (23.5-fold less active than benznidazole).
Finally, on amastigotes infecting J774 cells, 15-fold lower activity than benznida-
zole was found (Petray et al. 2004 ). According to the classical interpretation, these
in vitro data should rule out the etanidazole as trypanocidal agent. However, we
showed that this poor performance could be rescued without modifying its chemi-
cal structure just by encapsulating the drug in pH-sensitive liposomes. The example
of etanidazole, that in vivo proved to be less toxic than benznidazole, could be
extensive to other trypanocidal drugs. Mice infected with 10 2 trypomastigotes
(Tulahuen strain) and treated with liposomal etanidazole at 3.2 mg/mouse led to the
complete elimination of parasitemia. The administration of an equivalent dose of
empty liposomes (293 mg liposomal lipid/mouse) or free etanidazole had no effect
on parasitemia (unpublished results). The etanidazole liposomal therapy however,
remains to be tested against higher infecting inoculums from different T. cruzi
strains, both in the acute and the chronic stages of the disease.

9 Toxoplasma Gondii

Toxoplasmosis is primarily acquired through the ingestion of food or water con-
taminated with oocysts or undercooked meat infected with tissue cysts of the para-
site Toxoplasma gondii (Dubey 2004 ). It can also be transmitted from mother to
fetus, after mother acquisition for the first time during gestation, or by organ trans-
plantation. After ingestion, bradyzoites released from the cysts, or sporozoites
released from oocysts enter intestinal tissues and convert into taquyzoites. During
the usually asymptomatic acute phase, tachyzoites multiply inside the parasito-
phorous vacuola in the epithelial cells from the intestine. Tachyzoites propagate to
mesenteric ganglia and invade macrophages and nucleate cells by lymphohae-
matogenous via. Nearly after 10-14 days of acquisition, the immune system from
the host controllates the infection. In this point the parasite differentiates to a meta-
bolically quiescent bradyzoite and are found in cyst more prevalent in neural and
muscular tisúes, including the brain, eyes, and skeletal and cardiac muscles. Cysts
grow and remain inside the cells while bradyzoites multiply by endodyogeny
(Duval and Leport 2001 ). Brain cysts are spherical, rarely beyond 70 mm radii,
while in muscle are found ~100 mm length elongated cysts. Cyst wall produced by
modifications in the PV is elastic and thin lacking of glycogen and other polysac-
charides and encloses hundreds of bradyzoites. These cysts remain dormant in the
tissue until they can become reactivated. The host's innate immune system acts
against these cysts to prevent their reactivation in normal, healthy conditions,
although it's unclear by which mechanism this is managed. Evidence suggests that
cysts periodically are disrupted and the released bradizoites are destroyed by host's
immune system (Djurkovic-Djakovic et al. 2000 ). However, the immune systems
of immunosuppressed patients may fail to keep these cysts from reactiving, allow-
ing a full-blown reinfection to occur. The absence of antibodies in the brain makes
it more likely for cysts in the central nervous system (CNS) to persist and not being