Zech Johanna, Gold Daniel, Salaymeh Nadeen, Sasson Netanel Cohen, Rabinowitch Ithai, Golenser Jacob, Mäder Karsten
Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle (Saale), Germany.
Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
Pharmaceutics. 2020 Jun 3;12(6):509. doi: 10.3390/pharmaceutics12060509.
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 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.
蒿甲醚是一种创新的青蒿素衍生物，可用于治疗疟疾、血吸虫病和其他疾病。然而，其低水溶性以及溶解后易降解的特性限制了该药物在临床实践中的应用。我们开发了一种自微乳化药物递送系统（SMEDDS），它易于生产（简单混合）且载药量高。除了已知的药用辅料（Capmul MCM、聚氧乙烯氢化蓖麻油HS15、丙二醇）外，我们还确定聚山梨醇酯ID 46是一种有益的新型辅料。通过动态光散射、电导率测量、流变学和电子显微镜对其物理化学性质进行了表征。即使在30℃下也实现了高储存稳定性。口服蒿甲醚SMEDDS制剂在感染小鼠体内具有高活性。即使在相对低剂量的药物下，也观察到感染小鼠肝脏中的成虫、虫卵被彻底清除，并且预防了有害肉芽肿的形成。这种新制剂具有加速蒿甲醚在血吸虫病和疟疾临床应用的巨大潜力。
