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Taking a ride on sugar

Association of chemical compounds creates the possibility of treating leishmaniasis with pills instead of injections

REGINA MILDER - ICB/USPLeishmania amazonensis: now combated orallyREGINA MILDER - ICB/USP

It is difficult to know whether it was a stroke of luck or an indication that laying a bet on the improbable is sometimes worthwhile. Biophysicist Frédéric Frézard, from the Federal University of Minas Gerais (UFMG), invested in his intuition and arrived at an oral formulation of pentavalent antimony, the medicine most used to treat leishmaniasis, an infection caused by protozoa of the Leishmania genus, which, in its bland form, produces sores in the skin and in cartilage like that in the nose and ear, and, in the more serious cases, affects the liver and the spleen. The tests with mice have shown that, if all works out well, antimony capsules may replace the painful injections, applied only under medical supervision in long courses of treatment, of up to one month.

“A formulation of antimony for oral use would facilitate the treatment, because people with leishmaniasis usually live in the countryside and have to travel to the city to take the injections”, says Frézard. In search of a solution, this biophysicist who swapped France for Brazil ten years ago had the idea of associating the antimony with a sugar molecule – cyclodextrin – already used to facilitate the absorption of medicines that repel water. Generally speaking, cyclodextrin is used because its structure, in the format of a hollow cone, attracts molecules that do not mix with water, like the anti-inflammatory piroxicam. Accordingly, like a ball of ice cream inside a cone, piroxicam becomes soluble in water, crosses the walls of the intestine and falls into the bloodstream.

With antimony, it is not so easy. If swallowed pure, it is not absorbed by the intestine. When applied by means of injections, it acts for twelve hours before being filtered by the kidneys and is eliminated in the urine, because of its capacity for bonding itself with molecules of water.

Versatile sugar
Frézard decided to use cyclodextrin in the opposite way to the habitual one, joining to a molecule that attracts water, instead of repelling it. The strategy worked. Frézard gave the antimony and cyclodextrin mixture orally to 25 mice, while another 25 were given pure medicine, also orally. Less than one hour later, the levels of antimony in the blood of the rodents from the first group were three times higher than those shown by the other animals, as is attested in an article published this month in the Antimicrobial Agents and Chemotherapy magazine.

To find out whether this formulation would combat the parasites of leishmaniasis, Frézard counted on help from a team from the Federal University of Rio de Janeiro. The researchers contaminated the ears of 20 mice with Leishmania amazonensis, the species of protozoon usually associated with cutaneous leishmaniasis in Brazil. Five animals were given antimony and cyclodextrin orally, five just antimony, orally, five were given antimony injections, and five, used for control, a mixture of water and salt. The result was that the medicine associated with cyclodextrin was just as effective as a double dose of antimony administered by means of injections. Frézard?s team is currently testing the association of cyclodextrin and antimony in therapy against visceral leishmaniasis, a more serious form of infection, which affects the spleen and the liver, and can be fatal when not treated.