Malaria, caused by single-celled parasites named plasmodia, is one of the most widespread infectious diseases in the world. According to estimates by the World Health Organization, there were around 229 million cases of the disease around the world and 409,000 people died in 2019. Africa is the most severely affected region.

Artemisone is a promising substance in the fight against the horrible disease, but the active ingredient has not yet been used because of its instability and the fact that it is not easily absorbed by the body. Now, a team from Martin Luther University Halle-Wittenberg (MLU) in Germany, Hebrew University of Jerusalem (HUJI) and Hadassah University Medical Center in the capital are responsible for an important advance – they have developed a very simple method for preparing the active ingredient that makes it easier to administer and store. T

The researchers report on their work in the journal Antimicrobial Agents and Chemotherapy under the title “Efficient Treatment of Experimental Cerebral Malaria by an Artemisone-SMEDDS System: Impact of Application Route and Dosing Frequency.”

Lab tests have already shown artemisone’s efficacy in combating harmful parasites. “Previous formulations have proven very costly to produce,” noted Prof. Karsten Mäder, head of the pharmaceutical technology group at MLU. His research group specializes in the design and production of drug carrier systems and aims to prepare active ingredients is such a way that optimizes various properties – for instance, efficacy, absorption in the human body and stability of the substance. “We have developed a new formulation of artemisone in which the active ingredient is mixed with other substances. This is a very simple process that leads to a much more stable form. The process can be conducted in ordinary laboratories or factories,” added Mäder.

The new substance was tested against severe malaria on an animal model at HUJI and at Hadassah It was well absorbed by the body and was able to successfully fight off the parasites. A smaller amount than previous formulations was needed, which comes with an advantage: a lower dose means fewer side effects can be expected. In an earlier study, the team was also able to show that the new formulation of the drug is also very effective in treating schistosomiasis, a disease caused by flatworms. 

This disease is also widespread in the tropics, said Prof. Jacob Golenser who was a leader in the Jerusalem team. “Because complete cure of experimental cerebral malaria was achieved when using the optimal route of application, dose, and dosing interval, our formulation is altogether a promising, very versatile carrier for the delivery of ART in the treatment of severe or cerebral malaria,” he said.

“We developed a self-microemulsifying drug delivery system (SMEDDS) that overcomes these limitations,” the authors wrote. “Here, we demonstrate the efficacy of this formulation against experimental cerebral malaria in mice and the impact of its administration using different routes and frequency on the efficacy of the treatment. The minimal effective daily oral dose was 20 mg/kg. We found that splitting a dose of 20 mg/kg of artemisone given every 24 hours by administering two doses of 10 mg/kg each every 12 h, was highly effective and gave far superior results compared to 20 mg/kg once daily.” 

They obtained the best results with nasal treatment; oral treatment was ranked second, and the least effective route of administration was intraperitoneal injection. A complete cure of experimental cerebral malaria could be achieved through choosing the optimal route of application, dose, and dosing interval. Altogether, the developed formulation combines easy manufacturing with high stability and could be a successful and very versatile carrier for the delivery of artemisone in the treatment of human severe malaria, they continued.

Extensive clinical trials must be carried out before the active ingredient can be used as a medicine in humans. To this end, the team leaders are negotiating with several organizations that are committed to improving medical care in Africa.