Nanoparticles containing a natural substance treat visceral leishmaniasis with few side effects

A new therapeutic strategy developed by researchers at the State University of São Paulo (UNESP) could revolutionize the treatment of visceral leishmaniasis, a neglected tropical disease (NTD) transmitted by sandflies. Some 12 million people suffer from the disease worldwide and between 700,000 and 1 million new cases occur each year, according to the World Health Organization (WHO).

The technique developed by the researchers involved the use of lipid nanoparticles to deliver lupeol, a chemical compound known to kill the Leishmania protozoan parasites that cause the disease. Lupeol is a triterpene found in many vegetables and fruits, including mangoes, grapes and strawberries, green peppers and olives, for example.

In animal tests, the strategy was shown to eliminate Leishmania from affected organs. The results are reported in an article published in the journal Drugs.

There are three main forms of leishmaniasis. The visceral form is the most serious, with a mortality rate of up to 95% if untreated, and up to 10% even if treated, according to the WHO. The others are cutaneous leishmaniasis (the most common, usually causing skin ulcers) and mucocutaneous leishmaniasis (affecting the mouth, nose and throat).

Available treatments, based mainly on the use of pentavalent antimonials or amphotericin B, cause serious side effects, particularly affecting the heart, liver and kidneys. Some leishmaniasis drugs are extremely expensive, place a heavy burden on public health systems, and can create parasite resistance to drugs if administered inappropriately. The researchers therefore underline in the article the urgent need to find or develop new active compounds, some of which have been identified in plants.

In this study, researchers affiliated with the Institute of Biosciences of the Coastal Experimental Campus (IB-CLP) of UNESP in São Vicente created a new technique consisting of administering lupeol in lipid nanoparticles.

“It has been demonstrated in vitro that lupeol is capable of eliminating forms of Leishmania, but it is not very soluble in physiological solutions, which limits its bioavailability in vivo,” said Jéssica Adriana de Jesus, first author of the article and postdoctoral researcher. at the IB-CLP-UNESP.

“Putting it in lipid nanoparticles solves the problem by overcoming biological barriers, maximizing the therapeutic effect and delivering the drug to the targets, which in the case of visceral leishmaniasis are the spleen, liver and bone marrow. Nanocarriers are simply the delivery vehicle. When they reach the target site, with the correct pH, they open and release the drug.

For the first time

The experiments involved four groups of hamsters infected with Leishmania infantum and treated for ten days. The first group received only lupeol, the second received nanoparticles containing lupeol, the third received empty nanoparticles, and the fourth received only a placebo. Samples were then collected from the animals’ spleen, liver, blood and plasma for biochemical, pathophysiological and parasite load analysis.

As expected, lipid nanoparticles carrying lupeol were more effective than lupeol alone in eliminating visceral leishmaniasis parasites from the spleen and liver: administration of the nanoparticles with lupeol for ten days reduced the number of parasites 99.9%.

“In addition, animals treated in this way showed minimal histopathological alterations in the spleen and liver. For the first time, we have proven that this combination is very effective in treating the disease and constitutes a significant formulation whose use should be considered.”

The lupeol-containing nanoparticles were administered by intraperitoneal injection. The group now plans to develop a nanocarrier for oral administration, which would allow the patient to take the drug at home, as well as versions for the topical treatment of cutaneous leishmaniasis.