Oral Administration of Artemisone for the Treatment of Schistosomiasis: Formulation Challenges and In Vivo Efficacy
Johanna Zech,
Daniel Gold,
Nadeen Salaymeh,
Netanel Cohen Sasson,
Ithai Rabinowitch,
Jacob Golenser,
Karsten Mäder
Affiliations
Johanna Zech
Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle (Saale), Germany
Daniel Gold
Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel
Nadeen Salaymeh
Department of Microbiology and Molecular Genetics, The Kuvin Centre for the Study of Infectious and Tropical Diseases, The Hebrew University of Jerusalem, Jerusalem 9112002, Israel
Netanel Cohen Sasson
Department of Medical Neurobiology, Institute for Medical Research-Israel-Canada, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel
Ithai Rabinowitch
Department of Medical Neurobiology, Institute for Medical Research-Israel-Canada, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel
Jacob Golenser
Department of Microbiology and Molecular Genetics, The Kuvin Centre for the Study of Infectious and Tropical Diseases, The Hebrew University of Jerusalem, Jerusalem 9112002, Israel
Karsten Mäder
Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle (Saale), Germany
Artemisone is an innovative artemisinin derivative with applications in the treatment of malaria, schistosomiasis and other diseases. However, its low aqueous solubility and tendency to degrade after solubilisation limits the translation of this drug into clinical practice. We developed a self-microemulsifying drug delivery system (SMEDDS), which is easy to produce (simple mixing) with a high drug load. In addition to known pharmaceutical excipients (Capmul MCM, Kolliphor HS15, propylene glycol), we identified Polysorb ID 46 as a beneficial new additional excipient. The physicochemical properties were characterized by dynamic light scattering, conductivity measurements, rheology and electron microscopy. High storage stability, even at 30 °C, was achieved. The orally administrated artemisone SMEDDS formulation was highly active in vivo in S. mansoni infected mice. Thorough elimination of the adult worms, their eggs and prevention of the deleterious granuloma formation in the livers of infected mice was observed even at a relatively low dose of the drug. The new formulation has a high potential to accelerate the clinical use of artemisone in schistosomiasis and malaria.
