Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
Department of Microbiology and Molecular Genetics, The Kuvin Centre for the Study of Infectious and Tropical Diseases, The Hebrew University of Jerusalem, Jerusalem, Israel.
Antimicrob Agents Chemother. 2021 Mar 18;65(4). doi: 10.1128/AAC.02106-20.
Artemisone (ART) has been successfully tested and in animal models against several diseases. However, its poor aqueous solubility and limited chemical stability are serious challenges. We developed a self-microemulsifying drug delivery system (SMEDDS) that overcomes these limitations. Here, we demonstrate the efficacy of this formulation against experimental cerebral malaria in mice and the impact of its administration using different routes (gavage, intranasal delivery, and parenteral injections) 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 ART given every 24 h, 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. We 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 ART in the treatment of human severe malaria.
蒿甲醚（ART）已在几种疾病的动物模型中成功进行了测试。然而，其较差的水溶性和有限的化学稳定性是严重的挑战。我们开发了一种自微乳药物传递系统（SMEDDS），克服了这些限制。在这里，我们证明了该配方对实验性脑型疟疾的疗效，以及通过不同途径（灌胃、鼻内给药和注射给药）和频率给药对治疗效果的影响。最小有效每日口服剂量为 20mg/kg。我们发现，将每日 20mg/kg 的蒿甲醚剂量分为两次，每次 10mg/kg，每 12 小时给药一次，非常有效，与每日一次 20mg/kg 相比，效果要好得多。我们通过鼻腔治疗获得了最佳效果；口服治疗排名第二，而最无效的给药途径是腹腔注射。通过选择最佳的应用途径、剂量和给药间隔，可以实现对实验性脑型疟疾的完全治愈。总之，所开发的制剂结合了易于制造和高稳定性，可作为一种成功且用途广泛的载体，用于输送 ART 治疗人类严重疟疾。
