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.
Bibliographical noteFunding Information:
The work was supported by the Deutsche Forschungsgemeinschaft [DFG grants GR 972/47-2 and MA 1648/12-2]. : We are grateful to Cipla (Mumbai, India) and Richard K. Haynes (North-West University, Potchefstroom, South Africa) for the supply of artemisone. We thank Manuela Woigk for her assistance with the HPLC analysis and gratefully acknowledge Gerd Hause for performing the cryogenic microscopy of our samples. We thank Lea Ann Dailey (University of Vienna, Vienna, Austria) and Foozie Sahne for discussions and manuscript reading.
Funding: The work was supported by the Deutsche Forschungsgemeinschaft [DFG grants GR 972/47-2 and MA 1648/12-2].
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