Biomedical Engineering Reference
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cleared as the protozoa in other tissues might have been. As a result, a strong rein-
fection in an immunocompromised state is often centralized in the CNS and can
lead to the severe pathogenesis associated with toxoplasmosis called toxoplasma
encephalitis that is lethal if untreated.
Congenital infections are more likely to be symptomatic and can be severe,
5-10% causing death, 8-10% severe brain and eye damage, 10-13% moderate-
severe visual impairments, 58-72% being asymptomatic at birth with some later
development of retino-choroiditis or mental impairments.
T. gondii
invades cells by pulling itself into the cell by mechanism simmilar than
Plasmodium
and lives in a simmilar PV.
Because of the short term and absence of clinical symptoms of the acute phase,
the main disease targets are the cysts in brain and muscle, both offering impaired
access to the medication.
9.1
Conventional Treatments
Due to the self-limited and benign nature of the disease, immunocompetent adults
do not receive treatment during the chronic phase of toxoplasmosis. Only are
treated those patients with reactivation by immunosuppression, with ocular lesions
or after acquisition by congenital transmission.
Firts line treatment is a sinergic combination of pyrimethamine and sulfadiazine
(a 4-amino-N-2-pirimidil-benzen-sulfonamida). Pyrimethamine interferes with
folic acid synthesis by inhibiting the enzyme dihydrofolate reductase (in mammals
and parasites) thus preventing the biosynthesis of purines and pyrimidines, thereby
halting the processes of DNA synthesis, cell division and reproduction. Sulfonamides
inhibit the dihydropteroate synthetase, a parasitic enzyme that participates in folic
acid synthesis from para-aminobenzoic acid. Hence, sulfonamides work synergisti-
cally with pyrimethamine by blocking a different enzyme needed for folic acid
synthesis. Pyrimethamine cause bone marrow supresión (and folic acid has to be
co-administered), hematologic toxicity, and/or life-threatening allergic reactions in
up to 50% of cases (Katlama et al.
1996
).
Clindamycine can substitute sulfadiazine in patient that do not tolerate sulfa
drugs. Spiramycin is recommended for prophylactic use during pregnancy.
These drugs however are not effective against cysts in brain and muscle
(Couvreur et al.
1991
; Djurkovic-Djakovic et al.
2000
).
9.2
Preclinical Delivery Systems
9.2.1
Targeted Delivery to Tachyzoites
Two approaches employed sulfadiazine as a single drug in the treatment of experi-
mental infection:
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